Histocompatibility

Abstract: Most of the polymorphic amino acids of the class I histocompatibility antigen, HLA-A2, are clustered on top of the molecule in a large groove identified as the recognition site for processed foreign antigens. Many residues critical for T-cell recognition of HLA are located in this site, in positions allowing them to serve as ligands to processed antigens. These findings have implications for how the products of the major histocompatibility complex (MHC) recognize foreign antigens.

Abstract: The three-dimensional structure of the class II histocompatibility glycoprotein HLA-DR1 from human B-cell membranes has been determined by X-ray crystallography and is similar to that of class I HLA. Peptides are bound in an extended conformation that projects from both ends of an 'open-ended' antigen-binding groove. A prominent non-polar pocket into which an 'anchoring' peptide side chain fits is near one end of the binding groove. A dimer of the class II alpha beta heterodimers is seen in the crystal forms of HLA-DR1, suggesting class II HLA dimerization as a mechanism for initiating the cytoplasmic signalling events in T-cell activation.

Abstract: The Story The Gene: Organismic Approach The Gene: Molecular Approach The Protein The Antibody The Cell Function The Population Sociology Evolution Index.

Abstract: Publisher Summary This chapter provides information on histocompatibility-linked immune response genes. The genetic study of the capacity to form specific immune responses has revealed that the recognition of antigens as immunogens by individual animals and inbred strains is governed by the product of individual dominant genes located in the genome in close relationship with the genes coding for the molecules bearing the major histocompatibility specificities. These genes are termed as “histocompatibility,” or “H-linked Ir genes.” The presence of relevant genes permit immune responses to be formed, characterized by cellular immunity and antibody synthesis against the determinants on the antigens concerned. Three types of antigens are most useful in the identification of H-linked Ir genes: (1) synthetic polypeptides with limited structural heterogeneity; (2) alloantigens that differ slightly from their autologous counterparts, and (3) complex multideterminants antigens administered in limiting immunizing doses in conditions where only the most immunogenic determinants are recognized. Thus, the discovery of specific H-linked Ir genes depends upon experiments wherein the immunological system is presented with a challenge of highly restricted heterogeneity and specificity. The chapter presents a description of the specific immune responses that are under the control of H-linked Ir genes in guinea pigs, mice, and rats.