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Immunology > Lecture 6 - MHC Intro > Flashcards

Lecture 6 - MHC Intro Flashcards

1
Q

Why is MHC important?

A
  1. Determines fate of engrafted/transplanted tissue

2. Highly polymorphic

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2
Q

Answer the following questions for:

  1. Class I HLA loci
  2. Class II HLA loci
  3. CLass III

1.What consists of the HLA (Human Leukocyte
Antigens)

  1. Where are they present?
  2. And they present antigen to which T-lymphocytes?

Which of these does not present antigen to T lymphocytes?

A 
1. Class I
HLA A
HLA B
HLA C
- present in all nucleated cells
- present CD8+ to T cells (cytotoxic/killer T cells)
  1. Class II
    HLA - D which has 3 subset loci: DR, DQ, DP
    - present in Antigen Presenting Cells (APC) like
  2. Dendritic
  3. B lymphocytes
  4. Macrophages
  • present CD4+ to T cells
  1. Class III
    - genes that happen to reside in MHC region but DO NOT PRESENT ANTIGEN
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3
Q

Where is the HLA complex found?

A

Short arm of chromosome 6

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4
Q

Answer the following for Class I Loci molecules (A,B,C)

  1. How many polypeptide chains does the loci code for?
  2. Are they associated non-covanetly with a lighter chain? What is this chain called if yes?
  3. What does the resulting cell surface molecule consist of?
  4. Which part of the Class I molecule is transmembrane?
A
  1. ONE polypeptide chain
    - 44,000 daltons
  2. Beta 2 Microglobulin , specified by a gene on another chromosome and NOT polymorphic
    • one alpha chain
      - Class I polypeptide
      - one light chain micro globulin Beta 2
  4. Alpha 3 is transmembrane
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5
Q

Which aspect of Class I molecule is polymorphic? Which part is the antigen binding site?

A
  1. Alpha 1 and 2 is polymorphic, beta 2 is NOT different in amino acid sequence
  2. Alpha 1 and 2 form the peptide binding cleft (supported y beta pleated sheet)
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6
Q

Answer the following for Class II HLA -D Loci molecules (subset DQ, DR, DP)

  1. How many polypeptide chains does the loci code for?
  2. Are they associated non-covanetly with a lighter chain? What is this chain called if yes?
  3. What does the resulting cell surface molecule consist of?
  4. Which part of the Class I molecule is transmembrane?
A
  1. Codes for 1 polypeptide chain, but 2 polypeptide chains per molecule
    - alpha chain
    - beta chain
  • together = 60,000 daltons
    2. NO lighter chain
    3. Consists of alpha 1 and beta 1
    4. Beta 2 and alpha 2 BOTH have a transmembrane C terminal portion)
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7
Q

Although the anchor molecules that bind a particular MHC Class I molecule do not need to be identical, they are always related.

In what way? (N terminal & C terminal)

A

N terminal = AROMATIC RESIDUE

C terminal = HYDROPHOBIC

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8
Q

Although the anchor molecules that bind a particular MHC Class II molecule do not need to be identical, they are always related.
HOW? State the 1st, 2nd, 3rd, and 4th anchor molecules

A

1st anchor - Hydrophobic

2nd - Negatively charged

3rd - Basic AA

4th - Hydrophobic

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9
Q

The genes that encode the MHC Class I alpha chains and the MHC Class II alpha and beta chains associate where? Where do they shuttle to?

A
  1. Associate in ER

2. Shuttle to cell surface to become membrane glycoproteins

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10
Q

What part of the MHC Class I gene is NOT encoded within the MHC region of chromosome 6?

A

Beta 2 - Microglobulin

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11
Q

Define what it means to express Class I and Class II genes in a codominant fashion of both chromosomes 6.

Discuss how haplotypes come into play and how they are expressed.

A

Each individual has 3 maternal and 3 paternal class I

AND has 3 maternal and 3 paternal class II molecular types

thus, each person has two “half sets” (haplotypes) of genes

  • one haplotype is inherited from each parent and are expressed equally

= CODOMINANT EXPRESSION of MHC ANTIGENS

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12
Q

The polymorphism in nucleotide sequence and thus amino acid sequence of the MHC allows for what?

A

Allow for various peptides to bind and various TCR’s to recognize the MHC

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13
Q

Which class of molecules binds short peptides of about 9 amino acids in length?

Long?

A
  1. Class I

2. Class II

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14
Q

Where are polymorphisms in the MHC molecule found specifically?

A

in the Peptide Binding Cleft

Class I – alpha 1 and alpha 2 have high variability
(alpha 3 has little to no variability)

Class II - alpha 1 and Beta 1 have high variability (not beta 2 tho)

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15
Q

In order for a cellular interaction to occur between a T cell and the MHC presented on a cell, what must be matched & recognized?

A
  1. Antigen

2. antigenic peptide on MHC molecule

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16
Q

What are cytolytic T lymphocytes (CD8) specific for?

T helper cells (CD4)?

A
  1. Foreign Ag products of CLASS I loci

2. Foreign Ag plus products of Class II loci

17
Q

What determines the specificity of the T killer cells?

A

Viral Peptide in the contact of a host cell’s CLASS I determinant!!

18
Q

What is the following called:

Lymphocytes interact with foreign antigen recognized by the lymphocyte in the context of host (self) MHC molecules

A

MHC Restriction

19
Q

What is MHC restriction important for? (2)

A
  1. Cytolysis of target cells by cytolytic T lymphocytes

2. T cell APC’s (macrophages, Dendritic cells, B cells) interacting with T cells in the production of CYTOKINES

20
Q

Each person has 2 haplotypes, with codominant genetic expression. Explain the statement

A

One haplotype is inherited from

each parent. Both of these haplotypes are expressed equally

21
Q

What is MHC restriction?

A

The dependence of the T cells specific reactivity on foreign Ag plus MHC products rather than on foreign Ag alone

22
Q

Each individual expresses how many maternal and paternal MHC types?

A

3 maternal and 3 paternal from Class I

3 maternal and 3 paternal from Class II

23
Q

Which part of the HLA complex is not encoded within the MHC region of chromosome 6?

A

B2 microglobulin

24
Q

Which varies in the different HLA-I molecules, B2 microglobulin or a chain?

A

a chain

25
Q

What part of the a chain of HLA-I crosses the cell membrane?

A

C-terminal fragment

26
Q

Summarize the general structure of a Class I HLA molecule.

A

The B2 microblobiulin and a3 domains support an interactive structure formed by a1 and a2 domains. The interactive structure is a B-pleated sheet platform supporting 2 a helices which form a cleft for binding antigenic peptide fragments.

27
Q

Where are Class I MHCs present?

Where are Class II MHCs present?

A
  1. all nucleated cells

2. dendritic cells, B lymphocytes, macrophages

28
Q

What is the major histocompatibility complex?

What is the HLA complex?

A

A set of closely linked highly polymorphic genetic loci that play a central role in immune reactions.

a tightly linked gene cluster of cell surface glycoproteins in humans and other mammals that regulates immune cell interactions and evokes intense allograft rejection.

29
Q

Compare class I and class II gene products Class I:

A

Each loci codes for polypeptide chain of 44000 daltons. resulting molecule has 1 alpha chain and 1 light chain B2 microglobulin. B2 always the same but a chain varies. C-terminal fragment of a chain crosses membrane.
Class II:
2 chains per molecule: a chain and B chain.
bind longer peptides than Class I
More sets of anchor residues

30
Q

Describe the genes that constitute the major histocompatibility complexes

A

MHC gene products are generally closely linked and highly polymorphic.
Class I:
3 subsets (A-C) present on all nucleated cells. Present antigen to CD8+ T lymphocytes
Class II:
HLA-D subset. Found on dendritic cells, B lymphocytes, and macrophages. present to CD4+ lymphocytes.
Class III:
happen to reside in MHC region but do not present antigen.

31
Q

Each person has 2 haplotypes, with codominant genetic expression. Explain the statement

A

One haplotype is inherited from

each parent. Both of these haplotypes are expressed equally

Immunology (26 decks)

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