Abstract
The major histocompatibility complex (MHC) is a genetic region originally defined by graft rejection and now known to encode at least three classes of molecules which have important roles in the immune system. The MHC class I and class II antigens are both polymorphic two-chain cell-surface glycoproteins which are recognized by T lymphocytes. However, they are generally recognized by different subsets of T cells and have different functions, different tissue distributions and, by all available evidence, different structures1–4. Much is known about the detailed structure of the class I antigens (HLA-A, B, C in human; H–2K,D,L in mouse)5–7. The 44,000 (44K)-molecular weight (Mr) heavy chain consists of an amino-terminal extracellular region composed of three 10KMr (90 amino acid) domains, a small hydrophobic membraneous segment and a small hydrophilic intracellular carboxy-terminal domain. The two amino-terminal domains are polymorphic, bear the carbohydrate and have no sequence homology with immunoglobulin. The third domain, closest to the membrane, and the 11.6K light chain (β2-microglobulin) are highly conserved and have strong sequence homology with immunoglobulin. The structure of class II antigens (DR, DC1 in human; I–A, I–E in mouse) is much less well understood. Previous experiments involving papain proteolysis of native DR antigen have shown that both the light and heavy chains have a large glycosylated amino-terminal extracellular region, a small hydrophobic membranous region and a small carboxy-terminal hydrophilic region8. We have now applied limited proteolysis to demonstrate that the extracellular region of the light chain consists of two domains, each with a disulphide loop. The amino-terminal domain bears the carbohydrate and is polymorphic, while the carboxy-terminal domain is relatively conserved and has significant amino acid sequence homology with immunoglobulin. These results suggest a new picture of class II antigens indicating strong structural similarities to both class I antigens and immunoglobulins.
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Kaufman, J., Strominger, J. HLA-DR light chain has a polymorphic N-terminal region and a conserved immunoglobulin-like C-terminal region. Nature 297, 694–697 (1982). https://doi.org/10.1038/297694a0
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DOI: https://doi.org/10.1038/297694a0
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