The MHC

Question 1

What is the general function of MHC, and what are the two types of MHC classes?

Answer 1

MHC presents peptide to T-lymphocytes

there are two classes, MHC Class I and MHC Class II

Question 2

What makes up the Class I loci, what do they do, and where is it expressed?

Answer 2

Class I loci includes HLA -A, -B, and -C

They are present on virtually all nucleated cells

present antigen to CD8+ T cells

Question 3

What makes up the Class II loci, what do the do , and where is it expressed?

Answer 3

Class II loci includes, HLA -DP, -DQ, -DR

These are found on dendritic cells, monocytes/macrophages, and B-lymphocytes

present antigen to CD4+ T cells

Question 4

Describe the structure of a Class I molecule

Answer 4

consists of one alpha chain with three alpha domains, alpha-1, -2, and -2 (the class I polypeptide), and a beta2 microglobulin

Question 5

Which domain of the Class I MHC is bound to the membrane?

Answer 5

the alpha-3 domain (C terminal) of the alpha chain

Question 6

describe the Ag binding cleft

Answer 6

A beta sheet that supports two alpha helices. Formed by the alpha -1 and -2 domains

Question 7

What is the difference in AA binding between class I and class II?

Answer 7

MHC class I bind peptides about 8-10 AA in length

MHC class II bind peptides about 13-17 AA in length

Question 8

Describe the structure of a Class II molecule

Answer 8

Each loci codes for a chain, with two chains per molecule

one alpha chain and one beta chain make up a MHC class II molecule, with two domains per chain (alpha-1, alpha-2 complexed with beta-1, beta-2)

Both the alpha and the beta chain have a TM domain

Question 9

describe the features of a peptide that binds Class I MHC

Answer 9

8-10 AA long

Has an anchor sequence at the amino terminus that must have a hydrophobic AA ((V)aline, (I)soleucine, (L)eucine)

Has an anchor sequence 1 AA away from the carboxy terminus that must be a t(y)rosine

Question 10

describe the feature of the AA anchor sequences of the Class II MHC

Answer 10

first anchor sequence must be hydrophobic

second anchor sequence must be negatively charged

third anchor sequence must be basic

the fourth anchor sequence is also hydrophobic

Question 11

What is the mode of expression of MHC genes?

Answer 11

Both class I and class II genes on chromosome 6 are expressed in a co-dominant fashion

Question 12

How many class I and class II molecules can an individual express, and how many total MHC?

Answer 12

6 Class I and 6 class II (3 from mom, 3 from dad for each), and thus 12 types of MHC total

Question 13

How does a T cell respond to Ag?

Answer 13

It must recognize Ag in the context of an MHC molecule that is presenting it to the T cell

Question 14

define MHC restriction

Answer 14

dependence on T cell reactivity to Ag plus MHC instead of to Ag alone

Question 15

give two examples of cellular interactions in which MHC restriction is important

Answer 15

cytolytic T cells killing target cells

APCs (dendritic cells, B lymphocytes, macrophages) interacting with T-lymphocytes associated with T-lymphocyte production of cytokines

Question 16

What domains of the MHC class I and II molecules bind Agenic peptide?

Answer 16

Class I: alpha-1 and alpha-2

Class II: alpha-1 and beta-1

Question 17

What would a T cell recognize?

Answer 17

Antigenic peptide and the two alpha helices of either alpha-1 and alpha-2 (MHC I) or alpha 1 and beta-1 (MHC II_

Question 18

What is important about MHC variability?

Answer 18

It is highly polymorphic which allows for the presentation of a wide variety of peptide, so if a pathogen mutates it can accommodate that and mount an effective immune response

Question 19

why do MHC molecules induce such a strong response?

Answer 19

They are viewed as foreign antigens, and therefore if an organ is transplanted into another individual, the host will view it as foreign and mount an immune response against it

Question 20

Which gene is not as polymorphic as the others?

Answer 20

DR alpha chain

Question 21

where are the polymorphisms located?

Answer 21

the peptide binding cleft - therefore mainly in the MHC Class I alpha -1 and -2 and in the MHC class II beta-1 domains