Immunology. Supplement最新文献

There is no doubt that HLA-DR molecules are acting as the products of HLA-linked immune response genes (Ir-genes), because (i) HLA-DR molecules are the restriction elements in the interaction between CD4+ helper T cells and antigen-presenting cells (APC) to respond to many antigens such as streptococcal cell wall antigen (SCW) (Nishimura & Sasazuki, 1983; Sone et al., 1985; Hizayama et al., 1986), schistosomal antigen (Sj) (Hirayama et al., 1987), Mycobacterium leprae antigen (ML) (Kikuchi et al., 1986) and so on; and (ii) anti-HLA-DR monoclonal antibodies completely abolish the immune response to those antigens (Nishimura & Sasazuki, 1983; Sone et al., 1985). However, genetic analysis of the immune response to those antigens in families or populations revealed that responsiveness is recessive and non-responsiveness to those antigens is a dominant genetic trait that is tightly linked to HLA (Sasazuki et al., 1980a, 1983; Watanabe et al., 1988). This is completely opposite to the situation under the Ir-gene control where responsiveness is dominant and non-responsiveness is recessive. In this paper, we report evidence of how we came across the concept of HLA-linked immune suppression genes (Is-genes) besides Ir-genes, and show evidence for the epistatic interaction between HLA-DR and DQ to determine the immune response to several antigens in humans.

The period of intellectual history of immunology that we wish to treat began some 30 years ago, in 1958, when the features of immune tolerance had already been described (Billingham, Brent & Medawar, 1953), but mechanisms remained difficult to fathom. The subsequent 30 years in quest of the key(s) to tolerance can be roughly divided into the pre-T-cell suppression half, and the years from 1973 to 1988 in which the major rival to ideas of clonal deletion or abortion has been the T-suppressor cell.

The manner in which minor histocompatibility (H) antigens have been defined in mouse and man, in vivo and in vitro, is considered. Chromosomal mapping of minor H genes using T-cell clones is illustrated, with particular reference to the H-Y antigen gene, using the sex-reversing translocation Sxr of mouse and the Sxr' mutation derived from it. A number of minor H antigen-specific T-cell clones restricted by class I or class II major histocompatibility complex (MHC) molecules are described, together with information about their phenotypes and T-cell receptor usage.

There are two important questions concerning the T-cell antigen receptor. Firstly, what is the structural basis of major histocompatibility complex (MHC)-restricted recognition? Secondly, what is the origin of tolerance to self-MHC and the 'learning' of MHC-restricted recognition during thymus development? These central questions are discussed here in the context of our current knowledge of the structures of the genes encoding T-cell receptor proteins, their expression during thymocyte development and the mechanisms by which the T-cell receptor repertoire is generated.

Despite the wealth of information concerning the structure of the antibody-combining site and the interactions involved in the binding of small molecule haptens, there is considerable debate about the way in which antibodies recognize and bind to the surfaces of foreign proteins. Two recent crystallographic analyses of antibody molecules complexed with protein antigens have provided the first glimpses of the nature of this interaction at the atomic level.

Monoclonal antibodies (mAbs) have identified further heterogeneity within the major CD4 and CD8 T-lymphocyte subsets. Antibodies to different polypeptides of the CD45 complex separate two largely non-overlapping subsets that may represent stages in the maturation of T cells or separate functionally distinct subsets.