MHC Class II genes include HLA-DP, HLA-DQ, and HLA-DR. The antigens encoded by these genes are found only on a few specialized cell types, including macrophages, dendrite cells and B cells, all of which are professional antigen- presenting cells (APCs).

Hence unlike class I molecules, only certain specialized cells can present antigens with class II molecules. They are particularly important in humoral immunity.

Class II Molecules

Class II molecules are heterodimeric glycoproteins, with 34kD alpha chain (about 230 amino acids) and 29kD beta chain (about 240 amino acids), both anchored in the membrane.

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Unlike class I molecules both alpha and beta chains of class II molecules are encoded by the MHC. Each of these two chains has 2 extracellular domains, together with the trans membranous and cytoplasmic domains.

The membrane-proximal alpha 2 and beta 2 domains are homologous to immunoglobulin CH domain (Refer chapter 6 for immunoglobulins). The two chains interact to form a groove at their outer end which, like class I molecules, always contains a fragment of antigen.

But the fragments bound to class II molecules are derived from foreign antigens that the cell has taken in from its surroundings. They present the foreign antigen to helper T-cells, which stimulate B-cells to elicit an antibody response. Unlike class I molecules, the foreign antigen (peptide) presented by class II molecules are derived from extracellular proteins and it is longer (aboutl5 to24 amino acid residues) than the peptide presented by the class I molecules.

Like Class I MHC, there are hundreds of alleles that make up the class II HLA gene pool. Class II molecules interact exclusively with CD4 + (helper) T cells. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules.