Major Histocompatibility Complex (MHC) Antigens

Question 1

MHC or Human Leukocyte Antigens (HLAs)

Answer 1

• controls adaptive & some innate immune responses.
• central importance in many immune-mediated diseases.
• strongest immunologic obstacle to all types of allografts.

Question 2

HLA molecules include 2 major isoforms:

Answer 2

1. Class I
2. Class II

• all encoded in the MHC complex of chromosome 6

Question 3

HLA molecules - 2 major isoforms are encoded where?

Answer 3

All encoded in the MHC complex of chromosome 6 & spans approx. 3.5 million base pairs on the short arm of chromosome 6.

Question 4

The immune system has evolved to recognize & to eliminate invading pathogens.
Key to this ability is due to?

Answer 4

• the interactions between 2 molecules:
  1. Major Histocompatibility Complex (MHC)
  2. T-cell receptor (TCR)

Question 5

MHC is a family…

Answer 5

of cell surface molecules found in almost all vertebrates.

Question 6

MHC molecules present a selection of peptides made:

Answer 6

• inside the cell (MHC class I)
• from endocytosed particles (MHC class II)

Question 7

MHC class I

Answer 7

• expressed by almost all nucleated cells.
• allows CD8+ (killer cells) T cells to scan the intracellular environment of the cells for threats.

Question 8

MHC class II

Answer 8

• expressed by professional antigen-presenting cells.
• allows CD4+ (helper cells) T cells to detect & to respond to extracellular pathogens.

Question 9

Difference between CD8+ & CD4+ T cells

Answer 9

CD4 T cells are MHC-II restricted and pre-programmed for helper functions, whereas CD8 T cells are MHC I-restricted and pre-programmed for cytotoxic functions.

Question 10

MHC Antigens normal function

Answer 10

• to help Tcells recognize that an antigen is foreign or not self.

Question 11

Types of MHC Antigens:

Answer 11

1. Class I MHC (MHC-I)
   - molecules are built into the plasma membranes of all body cells except RBC.
   - all nucleated cells
2. Class II MHC (MHC-II)
   - molecules appear on the surface of antigen-presenting cells (APCS) = dendritic cells, macrophages, B cells.

Question 12

Major Histocompatibility Complex (MHC)

Answer 12

• a genetic locus that controls histocompatibility.

Question 13

Define gene & where it’s found

Answer 13

• Gene = a segment of DNA that codes for a particular protein (trait).
• found on a particular location on a chromosome called a locus.

Question 14

MHC is polygenic & polymorphic
- Define polygenic

Answer 14

• a characteristic that is influenced by 2 or more genes.
  (multiple genes are involved & don’t follow the patterns of Mendelian inheritance)

Question 15

MHC is polygenic & polymorphic
- Define polymorphic

Answer 15

• presence of 2 or more variant forms of a specific DNA sequence that can occur among different individuals or populations.

Question 16

MHC Class I contains genes…

Answer 16

encoding 6 MHC proteins.

Question 17

MHC Class II contains…

Answer 17

a variable number of genes that ultimately encode 3 heterodimeric MHC proteins.

Question 18

Class I (MHC-I) region contains…

Answer 18

• contains 6 genes = of these are HLA-A, HLA-B & HLA-C.

Question 19

Classical class I genes

Answer 19

• HLA-A, HLA-B & HLA-C.
• are highly polymorphic, with each having thousands of possible variants or alleles.
• they encode the heavy (or alpha) chains of molecules that present antigen to CD8+ T cells.

Question 20

Principal class I-like genes

Answer 20

HLA-E, HLA-F & HLA-G

Question 21

Mutations in the HLA-A gene

Answer 21

• are associated with hemochromatosis = a disorder that causes the body to absorb excessive amounts of iron from the diet.

Question 22

Non-classical Class I genes
or
Class Ib genes

Answer 22

• encoded by these genes don’t present antigen to Tcells but are instead recognized by natural killer (NK) cells.

Question 23

MHC locus consists of ______ regions.

Answer 23

3

Question 24

MHC locus - 3 regions

Answer 24

1. Class I (most important) - contains genes encoding 6 MHC proteins.
2. Class II - contains a variable number of genes that ultimately encode 3 heterodimeric MHC proteins.
3. Class III

Question 25

Class II region

Answer 25

• encodes a number of HLA-D genes.
• some genes involved in antigen presentation that are NOT expressed at the cell surface.

Question 26

Classical class II genes

Answer 26

HLA-DP, HLA-DQ & HLA-DR
- each of these comprises a less polymorphic alpha chain & is expressed together with a highly polymorphic beta chain.
- the heterodimeric complex (formed by the assembly of 2 proteins) presents antigen to CD4+ T cells.

Question 27

Class III region

Answer 27

• Genes are very diverse here = some encode:
• complement system molecules (C4, C2, factor B)
• enzymes
• cytokines
• heat shock proteins
• molecules involved in antigen processing.
• There are no functional or structural similarities between the gene products encoded in the class III region (unlike the molecules encoded in the class I & II regions).

Question 28

HLA - serological vs genotypic definition

Answer 28

• Serological definition = defines HLA by the sequence of the genes that encode them.
• Genotypic definition = defines HLA by the precise amino acid sequence of the genes.

Question 29

MHC restriction

Answer 29

• T cells recognize antigens only in the context of MHC.

Question 30

Genetic variations in MHC molecules affect:

Answer 30

• the ability to make an immune response leading to resistance or susceptibility to infectious diseases, autoimmune diseases & allergies.

Question 31

Why is MHC polymorphic?

Answer 31

-