Several genetic loci appear to be involved in susceptibility to autoimmune disease. Some loci are disease specific, whereas others appear to exert a general effect on the autoimmune disease process. Despite a large number of studies of many different diseases, consistent associations with multiple autoimmune disorders have been restricted to three gene regions: the human leukocyte antigen (HLA) class II region on chromosome 6p21, the gene encoding cytotoxic T lymphocyte-associated 4 (CTLA-4) on chromosome 2q33, and the PTPN22 gene encoding lymphoid tyrosine phosphatase (LYP) on chromosome 1p13. Each of these loci is likely to encode molecules that are crucial in the immune cascade and are actively involved in T-cell activation. Moreover, gene polymorphisms that affect function might contribute to the triggering of autoimmune disease by as-yet-unknown mechanisms. This review summarises recent developments and current understanding of the way in which molecules encoded by these susceptibility loci contribute to T-cell activation, and hypothesises how aberrant function of these molecules might trigger autoimmunity.

The major histocompatibility complex (MHC) harbours genes whose primary function in regulating immune responsiveness to infection is to present foreign antigens to cytotoxic T lymphocytes (CTLs) and T helper cells. In the case of infection by human immunodeficiency virus (HIV), defining the optimal HIV epitopes that are recognised by CTLs is important for vaccine design, and this in turn will depend on the characteristics of the predominant infecting virus. Moreover, the particular MHC human leukocyte antigens (HLAs) expressed by a geographical population is important since these are likely to determine which HIV epitopes are immunodominant in the anti-HIV immune response. Consideration of these aspects has lead to the dawn of a new era of MHC-based vaccine design, in which the CTL epitopes are selected on the basis of the frequency of restricting MHC alleles. This article reviews data on the distribution patterns of molecular subtypes of HLA class I and class II extended haplotypes, discussing distribution among Asian Indians but with reference to global distributions. These data provide a genetic basis for the possible predisposition and fast progression of HIV infections in the Indian population. Since there is selective predominance of different HLA alleles and haplotypes in different populations, a dedicated screening effort is required at the global level to develop MHC-based vaccines against infectious diseases. It is hoped that this might lead to the development of multivalent, poly-epitope, subtype-specific HIV vaccines that are specific for the target geographical location.

The human leukocyte antigen class I allele HLA-B27 is a major histocompatibility complex (MHC) antigen that is strongly associated with the spondyloarthritic group of human rheumatic diseases, the most commmon of which is ankylosing spondylitis. Although the mechanism underlying this disease association remains unknown, numerous theories have been proposed. Much more is known of the natural role of HLA-B27 in binding and presenting antigenic peptides to T cells. The ‘arthritogenic peptide hypothesis’ suggests that the role of HLA-B27 in disease relates to its specificity for binding certain peptides. Recently, it has also been shown that HLA-B27 has an unusual cell biology and can adopt a novel homodimeric structure. In this review, a molecular model of the HLA-B27 homodimer is presented and the possible pathogenic significance of such a structure is discussed.

Type 1 diabetes mellitus (IDDM) results from a chronic process of autoimmune destruction of ß cells of the Langerhans islets. The presence of autoantibodies (ICA, GADA, anti-IA2, IAA) in serum preceds the clinical onset of the disease. Genetic predisposition for IDDM is connected with HLA, CTLA-4 and insulin gene region.

The aim of the study was the genetic and immunological analysis of a triplet. One of them developed Type 1 diabetes mellitus. We analysed HLA class II, CTLA-4 and insulin gene polymorphisms in the whole family. Besides, we investigated immunological status of three brothers.

All patients present identical genotype for VNTR loci: D1S80, D17S5 and Apo B, as well as for HLA-DRB1, — DQA1, — DQB1, CTLA-4 gene and all studied insulin gene polymorphisms. That proves their monozigosity. The triplet presents strong genetic predisposition for IDDM. The two patients without overt diabetes have increased levels of ICA, GADA, IA2 and IAA.

A total of 71 pairs of like-sexed dizygotic twins were studied, comparing within-pair differences for plasma total, free and esterified cholesterol, and triglyceride with the number of HLA haplotypes the twins had in common. If associations are present between HLA and the blood lipids studied, the twins with no haplotypes in common would be expected to have the largest within-pair mean square, those with two in common the smallest, and those with one in common an intermediate value. No significant differences were found comparing within-pair mean squares for the variables studied.