Question

Description

Both Immunoglobulins and the proteins of the MHC complex are capable of recognizing a very broad range of proteins or peptides associated with pathogens. Their methods of establishing this wide repertoire of recognition is established at the genetic level, but have no similarities in the processes.

Instructions

Describe the genes of both these effectors, characterizing the steps in the generation of this diversity in Immunoglobulins. Describe the inheritance of MHC genes and how these genes are expressed and regulated. You should include your explanation of polygeny and polymorphism as it relates to the MHC haplotype of an individual, and also include explanation of affinity maturation and somatic hypermutation with your description of immunoglobulins.

Answer 1

Ans.

Immunoglobulins -

In nonlymphoid cells, the gene segments encoding the V region of an immunoglobulin chain are some considerable distance away from the gene segment encoding the C region. however, as B lymphocytes matures, gene rearrangement brings the V-region sequence nearer to the C region.

Steps in generation of diversity in immunoglobulins -

1 - V(D)J recombination - The Variable domain of an immunoglobulin heavy or light chain is encoded by more than one gene segment.

A heavy-chain V domain is encoded by three gene segments, namely V_H ,D_H and J_H and There are multiple different V-region gene segments. so, It is the random selection of just one gene segment of each type to assemble a V region that makes possible the great diversity of V regions.

similarly, A light-chain V domain is encoded by two gene segments, namely VL and J_L and there are  multiple different V-region gene segments for light chain as well. which further contibutes to diversity.

2 - different possible combinations of a heavy and a light chain in the complete immunoglobulin molecule.

first two steps contribute to combinatorial diversity

3-  addition and subtraction of nucleotides by the recombination process at the joints between different gene segments. (junctional diversity)

4-  point mutations into the rearranged V-region genes of activated B cells i..e., Somatic hypermutation creates further diversity that can be selected for enhanced binding to antigen.

5- Some of the B cells expressing mutant immunoglobulin molecules are preferentially selected to mature into antibody-secreting cells as they bind antigen better than the original B-cell receptors. this is called as Affinity Maturation.

MHC -

The major histocompatibility complex is located on chromosome 6 in humans, having more than 200 genes.

There are three class I ?-chain genes in humans, called HLA-A, -B, and -C. There are also three pairs of MHC class II ?- and ?-chain genes, called HLA-DR, -DP, and -DQ. Each individual has two complete sets of the six HLA molecules. One set is inherited from the father and another set from the mother. Each set of HLA molecules is called a haplotype.

Two separate properties of the MHC make it difficult for pathogens to evade immune responses . First, the MHC is polygenic i..e., it contains several different MHC class I and MHC class II genes, so that every individual possesses a set of MHC molecules with different peptide-binding specificities. Second, the MHC is highly polymorphic; that is, within the population, there are multiple variants of each gene.