Fundamentals I Test 4 Burrows – Flashcards

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In what two forms are Ab's found?
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Attached to B-cell membranes or Secreted by Plasma cells
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T/F; Edelman ; Porter used ultracentrifugation, Papain digestion, Pepsin digestion, ; Mercaptoethanol to break down IgG and discover it's structure.
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True
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What connects the heavy and light chains of IgG?
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Disulfide Bonds
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On what end of the light chain do you find the constant & variable regions?  In which region do you find kappa or lambda types?
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Constant: C-terminal, kappa & lambda

Variable: N-terminal

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How many basic sequence patterns are found on the heavy chain constant region?
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5
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What defines the isotype of an Ab?
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The heavy chain type (IgM, IgG, IgA, IgD, IgE)
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What are the Ag-binding sites of Abs, and where are they found?
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Hypervariable or Complementary-Determining Regions; on the variable portion of the heavy & light chains
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T/F  CDR's are not found adjacent on the primary structure, but they are adjacent in the secondary structure.
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True; they fold to be in the same area
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What is the term for the Ag Determinant binding site?
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Epitope
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What gives the Hinge region its flexibility, what is it susceptible to, and in what Ig's is it found?
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Flexibility - Proline Residues; Susceptible - Proteolytic Enzymes; IgG, IgD, and IgA
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What is the most abundant Ig in serum?  What is its structure?
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IgG; monomer of 2γ H-Chains and 2κ or λ L-Chains
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How many subclasses does IgG have & what makes them different?
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4 (numbered by their serum concentration); size of hinge region & number and position of interchain S-S bonds b/w H-chains
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Which Immunoglobulin molecule is pentameric and has 10 potential Ag-binding sites?
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IgM
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Which Ab is the first produced during primary immune response and is the Ag receptor on B cells?
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IgM
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What is the predominant Ig class in mucosal secretions?  In what forms does it exist?
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IgA; monomeric in serum & dimeric/tetrameric in secretions
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What is the main effector Ab in mucosal secretions, and how is it formed?
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S-IgA; IgA binds pIgR and is internalized, a portion is then cleaved leaving the other portion bound to IgA which forms S-IgA
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Which type of Ab mediates Type 1 hypersensitivity reactions and binds Fc receptor of basophils & mast cells?
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IgE
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What induces degranulation and releases histamine?
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Cross-linking or receptor bound IgE by Ag
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Which two Immunoglobulins are membrane-bound and co-expressed on mature B cells?
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IgD and IgM
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T/F  Multiple Ab's can recognize the same Ag because there are many different epitopes on a single Ag.
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True
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What is the Ab response to an Ag which induces a mixture of Abs to one Ag?; What does this result in?
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Polyclonal Ab Response; Ab heterogeneity = increases immune protection
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What is the Ab response to a single epitope?
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Monoclonal Ab (mAb)
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T/F; It is feasible to purify monoclonal Ab from polyclonal Ab.
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False; it is NOT feasible
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What two cells are fused in the preparation of mAbs?
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Ab-producing B cell ; plasmacytoma
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Describe the Ag-Ab Interaction.
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Reversible ; Non-covalent Van der Waals interactions
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What is defined as the measure of the strength of the binding ease of association or dissociation?
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Affinity
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What is defined as an increase in affinity due to multivalent binding or the summation of multiple affinities?
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Avidity
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What is a substance able to generate antibody or T cell responses?
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Immunogen
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What are the three most important characteristics of a good antigen?
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Size: larger is better

Chemical Composition: Proteins ; Carbohydrates ; Lipids

Similarity to self-antigens: multiple differences are better

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What is an important characteristic for T cell Ag response?
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Degradability
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What is the term for a Non-immunogenic substance, usually low molecular weight, that can induce Ab formation when coupled to a larger "carrier" molecule?
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Hapten
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Which three Hapten examples can you make monoclonal Ab's to?
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Cortisol, Estradiol, & Testosterone
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What is the term for Ab's binding Ag's & sticking together?
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Agglutination
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T/F  Antibodies can inhibit attachment of bacteria to cells.
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True
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What does a bacteria tagged with Ab's bind to on the macrophage cell surface?
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Fc receptors
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What is the term for any molecule that acts as a binding enhancer for the process of phagocytosis?
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Opsonization (via Fc Receptor)
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Is it typical to find a peptide on an MHC?; What are the two possibilities for it?
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Always has a peptide; usually from self, but if it is a foreign peptide it alerts T cells
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What are the four good Ag-Ab reactions In Vivo?
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Neutralization, Opsonization, Complement Lysis, ; Prevention of Adherence
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What test is used to see if a person has been infected with a virus such as HIV?
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Enzyme Linked ImmunoSorbent Assay; (ELISA); first line assay/preliminary test
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After an ELISA test is preformed what is done to determine which viral G's the patient has made Ab's to?
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Western Blot (second line assay)
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Is it possible to have Ab's without being exposed to a particular virus?
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Yes, because some viral Ag's are cross-reactive
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What is screened for in a pregnancy test?
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Human Chorionic Gonadotrophin; prevents Ab's from agglutinating
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After Ab binds Ag, the outcome depends on what?  What determines effector functions?
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Constant region of the heavy chain; Ab isotype
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At what level does diversity operate?
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lymphocyte level
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What causes isotype switching?
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Ag binding
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Describe the parts found in an original DNA sequence.  (as it relates to isotype switching)
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Leading Region, Variable Regions, Joining Regions, Constant Regions, and Introns
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Describe the parts of an mRNA strand.
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Leading region, Variable region, and Constant region (no introns)
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What is the process of splicing together segments of genes in order to generate tremendous diversity without monopolizing the genome?
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Ig or TCR gene rearrangement
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What are the segments found in light chains?
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κ and λ light chains each have; Leading, Variable, Joining, and Constant
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What are the segments found in heavy chains?
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Leading, Variable, Diversity, Joining, and Constant
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Describe the mechanism of Immunoglobulin Gene Recombination.
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(also called Somatic Recombination) Gene segment forms a loop that is then excised leaving the outer portions adjacent to each other
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T/F  Cells continue to proliferate between each step in Somatic Recombination resulting in even more possibilities for differentiation.
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True
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How many possible Ab's can be made?; How many different Ab's are produced by each B cell or plasma cell?
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3 million; only ONE
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What regulates Isotype Switching by Somatic Recombination?
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cytokines produced by T cells (T cells regulate B cells)
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T/F  Cells that do not undergo isotype switching may still respond to Ag.
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False; only cells that switch will respond to Ag
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In what order and what amounts are the immunoglobulins produced in a Primary Response?
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IgM followed by IgG in approximately equal quantities
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In what order and in what amounts are different isotypes expressed in a secondary response?
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IgM and IgG about the same time; much more IgG than IgM (b/c cell remembers how to make IgG)
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What is the Ag-binding portion of the T Cell Receptor?
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Variable alpha & beta regions
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Can TCR exist in secreted form?
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No, only as a transmembrane Ag receptor
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In what organ do TCR's undergo somatic gene recombination?
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Thymus
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What are the parts of the gene segment that codes for TCR variable region?
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Variable, Joining, Constant
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Can B cells recognize intact protein Ag's?  What about T cells?
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B cells - Yes; T cells - No (must be degraded)
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What results in autoreactive B and T cells that are not eliminated?
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Autoimmune Disease
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What can result from chromosomal translocations arising during VDJ recombination or isotype switching?
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Lymphoid Malignancies
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What are the major differences between B & T cell Ag Receptors?
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B cell: Immunoglobulin, B cell Transmembrane protein, plasma secreted effector

T cell: TCR, T cell Transmembrane protein, CD4 Th, CD8 Tc

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Where are proteins denatured to be presented?  What denatures them?
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Lysozyme; proteases
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T/F  B cell antibodies can operate at a distance.
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True
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Do B cells recognize intact Ag's or bound peptides?; What about T cells?
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B cells: Intact Ag's       T cells: degraded peptides on MHC
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T/F  Ag-specific T cell function requires MHC contact, but does not require cell-to-cell interaction.
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False; requires MHC and cell-to-cell contact
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What cells express MHC Class I?  To which cells do they present?
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All nucleated cells; CD8 T cells (Cytotoxic killer cells and kills virus infected cells)
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What cell have MHC Class II and to what cells do they present?
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APC's (dendritic cells, B cells, MQ's); CD4 T cells (T helper cells)
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What occurs after T helper cells are activated?
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B cells proliferate, differentiate, & isotype switch and help activate MQ's to kill intracellular pathogens
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How do CD4 T cells help B cells?
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T ; B cell form very close contact and T cell secretes IL-4 into the pocket b/w the cells to induce isotype switching in the B cell
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Is it possible for a B cell to express MHC class I and class II?
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Yes; if it is presenting an Ag
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Describe T cell screening.
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T cells go from cell to cell scanning the self-peptides on MHC Class I until it finds an MHC Class II with foreign Ag
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Is the peptide binding cleft found on the membrane proximal or distal domain of MHC classes I and II?
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Distal
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In what portion of the MHC does the peptide sit?; How does it differ between class I and II?
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Beta Sheets; MHC class I is surrounded on all sides by the MHC, Class II runs the full lenth of the MHC
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How does the structure of MHC differ between classes I and II?; What are the subclasses of each?
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Class I: 3 ; and 1 ; chain with A, B, ; C types

Class II: 2 ; and 2 ; chains with DP, DQ, ; DR types

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What is described as allelic variation in MHC genes and is concentrated in the peptide binding regions of Class I and Class II?
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MHC Polymorphism
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How many MHC genes does each individual inherit?
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9 maternal and 9 paternal
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What are the consequences of MHC Polymorphism?
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Organ tissue transplants are difficult; change peptide binding specificity of MHC; pathogens could mutate to avoid immune detection by MHC's
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