MHC Structure and Expression

Flashcards covering MHC structure, expression, and function based on lecture notes.

What type of antigens are displayed by MHC I? What type of T cell surveys
  What type of antigens are displayed by MHC I?  What type of T cell surveys antigens displayed by MHC I?

Displays endogenous antigens, primarily from intracellular pathogens, and is surveyed by CD8+ T cells.

What types of antigens are displayed by MHC II?  What type of T cell surveys antigens displayed by MHC II?

Displays exogenous antigens, primarily from extracellular pathogens, and is surveyed by CD4+ T cells.

What kinds of proteins are encoded by MHC III genes?

Encode various proteins involved in immune system functions, including components of the complement system.

Factor B, C2, and C4

   What domains of MHC I form the peptide binding groove?

Formed by the alpha-1 and alpha-2 domains.

What domains of MHC I interact with CD8?

MHC I interacts with the CD8 co-receptor through its alpha-3 domain.

  What domains of MHC I interact with CD8?

Formed by the alpha-1 and beta-1 domains.

   What domains of MHC II interact with CD4?

MHC II interacts with the CD4 co-receptor through its beta-2 domain.

  Why can MHC II bind longer peptides than MHC I? 

MHC II can bind longer peptides due to an open-ended binding groove.

Size range of peptides for MHC I

8-11 amino acids.

Size range of peptides for MHC II

13-25 amino acids.

What are the roles of the anchor amino acids in the peptide associated with MHC I? 

Key residues that secure the peptide in the binding groove, typically located at the termini of the peptide. Generally hydrophobic at carboxy terminus.

What is the conformation of the peptide in the binding groove of MHC I? Binding nature?

The peptide is presented in a closed conformation.

Binding nature: extended structure where both ends interact with the MHC groove, but the middle arches up and away from the MHC molecule.

    How does the conformation of the peptide bound by MHC I compare to the conformation of the peptide bound by MHC II?

MHC II presents peptides in an open conformation, allowing for more extensive interactions.

Binding nature: Held at constant elevation

  What amino acids interact with the peptide binding groove of MHC II? **********

Typically include residues that fit into specific pockets of the MHC II binding groove.

How many different alleles for MHC I and II exist throughout the human population?

100’s

How many different alleles for MHC I and II does an individual possess? ******

An individual generally possesses 6 MHC class 1 alleles . 1 HLA - A, B,C from each parent

six to eight MHC class II alleles (one HLA-DP and -DQ, and one or two HLA-DR from each parent, and combinations of these).

  Where does most of the variation between alleles occur?

Most variation occurs in the peptide-binding region of the MHC genes.

    How are the genes in the MHC locus inherited?  What is meant by a haplotypes?

MHC genes are inherited in a linked fashion as haplotypes, rarely undergo recombination due to the genes within the loci being extremely close together. (inherited as a group)

is recombination between alleles in the MHC locus common?  Why or why not?

-Recombination is rare due to strong linkage of MHC alleles, (inherited together) and close proximity.

  What does it mean to have codominant expression of alleles?

Both maternal and paternal alleles are expressed simultaneously in an individual. MHC genes are codominant.

   Does a single cell display one specific variation of MHC on its surface or more than one?

A single cell typically displays multiple variations of MHC on its surface. - Allows presentation of a wide variety of peptides.

   What does it mean to say cells/individuals have heterozygous expression of MHC?

Having two different alleles at a given locus, leading to a diverse range of MHC molecules. It is unlikely to find a homozygous individual due to large allele variety.

    What expression pattern indicates a health cell?

Cells exhibiting balanced MHC expression, presenting self and non-self antigens appropriately, typically indicate health.

Notes:

• Self MHC 1/Self peptide: Healthy

Infected cell expression pattern

Enhanced expression of MHC I and potentially MHC II.

Notes: Self MHC 1/non--self peptide = infected cell

Self MHC 2/ non self peptide = body is infected

a How does MHC/peptide expression help maintain self tolerance?

Essential for positive and negative selection of developing T cells in the thymus.

self MHC 1 and 2 / self -peptides

      How does MHC/peptide expression help maintain self tolerance?

Through displaying self-peptides, MHC prevents autoimmunity.

• self peptides in MHC 1 and MHC 2

What cells express MHC 1? Which don’t?

Expressed by all nucleated cells; absent in red blood cells and certain other cells. Does not display in non nucleated cells.

MHC I expression variation by cell type:

Expression levels can differ; some cells express high while others express low levels

• highest: lymphocytes

• Low: some neurons, liver cells, fibroblasts, muscle cells

  Will two individuals infected with the same pathogen display the same peptides with MHC I?  Why or why not?  What effect will this have on the immune response to the pathogen?

Different individuals may present different peptides due to genetic diversity in MHC alleles, this can lead to individuals having varying immune responses/ being more or less susceptible to certain pathogens, varied immune responses among individuals.

What happens to a nucleated cell that does not display MHC 1/peptide complexes?

• Killed by NK cells

a  What cells constitutively express high levels of MHC II?

Dendritic cells

What cells constitutively express high levels of MHC II?

Macrophages - B cells?

    Can non-professional APC’s display antigen with MHC II?  If so, under what circumstances and for how long?

Can express MHC II under specific conditions, typically limited to the presence of inflammatory signals. Activation of transcription factors - CITA up reg class 1, CIITa up reg class 2. Ex: glial cells, fibroblasts.

Role of CITA and CIITA in MHC expression

Key transcription factors regulating the expression of MHC genes - upregulates class 1 and 2.

  Describe examples of how viral infections can affect MHC expression.

Certain viruses can down-regulate MHC expression to evade immune detection.

Ex: cytomegalovirus prevents MHC 1 assembly, adenovirus 12 decreases TAP 1/2 transcription which helps load peptides and is involved with presentation.

What cytokines can increase MHC expression? 

IFN’s and TNF upregulate MHC expression. (INF gamma, alpha, and Tumor necrosis factor alpha.)

Cytokines decreasing MHC expression

Certain cytokines like IL-10 can suppress MHC expression. like MHC 2

corticosteroids, prostaglandins (also immunosuppressants)

Determinant selection model

Describes how T cells only recognize peptides that fit specific MHC types - some peptides are more crucial for responsiveness than others, some haplotypes are more beneficial than others.

Holes in the repertoire model

Explains variability where certain peptides are not presented due to MHC restrictions - (if some tcr bind a peptide too tightly that may be similar to a self-peptide it will not be used - leaving potential immunity hole)

Comparison of determinant selection and holes model

Both models illustrate how MHC diversity leads to individual variations in immune response.