Dr. P. Mary AnupamaMSc,Ph.D

St. Joseph’s College for Women, VisakhapatnamEmail. Id : drmaryaunpama@gmail.com

IMMUNOLOGY

CONTENTS❖INTRODUCTION

❖GENERAL ORGANIZATION

❖GENE PRODUCTS OF HLA

❖STRUCTURE OF HLA MOLECULES

❖CELLULAR DISTRIBUTION

INTRODUCTION

• MHC represents cluster of genes present on cells of mammalian species

• Their role- Intercellular recognition and in discriminating self-cells from non-self.

• T- cells recognize antigens when presented by MHC molecules.

• MHC act as Antigen presenting elements.

• There are 2 T cells populations- T cytotoxic cells that recognize antigens when

presented by Class I MHC molecules and T helper cells that recognize antigens

presented by MHC class II molecules.

General organization of MHC molecules

• Major histocompatibility complex

represents a cluster of genes which

are present as a continuous stretch

on chromosome 6 in human being

and chromosome 17 in mice.

• In human beings, the MHC is called

HLA- Human Leucocyte Antigen,

while in mice it is called H-2

complex.Figure 1. Location of HLA complex in Human

(source- https://en.wikipedia.org/wiki/File:HLA.svg)

Types of MHC molecules

1) Class I MHC genes: These gene encode for glycoproteins and are expressed on

almost all nucleated cells. Their products present antigenic peptides to T

cytotoxic cells.

2) Class II MHC genes: These encode for glycoproteins expressed on Antigen

Presenting cells (Macrophages, dendritic cells and B-cells), and they present

processed Antigenic peptides to T helper cells.

3) Class III MHC genes: These encode for other proteins which are secreted out.

They are mostly complement proteins and molecules involved in inflammatory

responses.

Inheritance of MHCThe MHC genes are linked together and the genes which are inherited by a person formone parent in known as Haplotype. An individual expresses both the maternal andpaternal MHC gene products on their surface (figure 2).

Figure 2. Codominant expression of MHC genes

(By derivative work: Zionlion77 (talk)MHC_Class_1.svg: User

atropos235 on en.wikipediaMHC_Class_2.svg: User atropos235

on en.wikipedia - MHC_Class_1.svgMHC_Class_2.svg, CC BY-

SA 3.0,

https://commons.wikimedia.org/w/index.php?curid=5658669)

• Gene products of HLA: There are 3 classes of HLA genes, I, II and III.

Complex HLA

MHC

ClassII III II

Regions DP DQ DR C4, C2, BF B C A

Gene

products

DP

a,b

DQ

a,b

DR

a,bC protein

TNF-a

TNF-aHLA-B HLA-C HLA-A

Structure of MHC molecules- MHC Class I

Figure 3. MHC Class I molecule

(Edited from source- By User atropos235 on en.wikipedia - Own work, CC BY 2.5,

https://commons.wikimedia.org/w/index.php?curid=1805424)

Structure of MHC molecules- MHC Class II

Figure 4. MHC Class II molecule

Distribution of MHC molecules- MHC Class I

• These are present on almost all nucleated cells.

• They constitute to around 1% of proteins of plasma membrane which accounts to around

5 x 105 molecules per cells.

• These are responsible for graft rejection.

• Liver cells exhibit lowest of MHC proteins on their surface and hence these

transplantations are always successful, while sperm cells lack MHC molecules and

hence, they are not rejected.

Distribution of MHC molecules- MHC Class I

• A normal cell always expresses self-peptides onto the surface of MHC molecules

which are out of their degradation.

• These help the immune system to monitor transformed cells and virally infected

cells.

• These cells will either express a new protein (mutated one) or a viral peptide.

• Such cells are recognized by T cytotoxic cells and eliminated.

Antigen

presenting cells,

primarily

dendritic cells,

Macrophages, B

cells and thymic

epithelial cells

Increased

expression of

MHC

CYTOKINES

Distribution of MHC molecules- MHC Class II