Insulin-specific human T cells. Epitope specificity, major histocompatibility complex restriction, and alloreactivity to a diabetes-associated haplotype

• Published in: The Journal of immunology (1950) Vol. 139; no. 11; pp. 3622 - 3629
• Main Authors: Miller, GG, Pollack, MS, Nell, LJ, Thomas, JW
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.12.1987; American Association of Immunologists
• Subjects: Animals; Biological and medical sciences; Cattle - immunology; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epitopes - immunology; Humans; Insulin - immunology; Isoantigens - immunology; Lymphocyte Activation; Management. Various non-drug treatments. Langerhans islet grafts; Medical sciences; Species Specificity; Swine - immunology; T-Lymphocytes - immunology; Endocrinopathy; Human; Antigen presentation; Immune response; Antigenic determinant; Diabetes mellitus; Major histocompatibility system; HLA-DR»-System; In vitro; Insulin; Immunogenetics; Specificity; Alloantigen; Cell line; Treatment; T-Lymphocyte; Haplotype
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.139.11.3622

T cells from an insulin-treated diabetic (ML, HLA DR1, w6) were stimulated in vitro with insulin, cloned at limiting dilution, and examined for their fine specificity and genetic restriction. T cell lines (TCL) derived from beef insulin stimulation were highly specific for epitopes on beef insulin, whereas pork insulin stimulation generated T cells that recognized determinants shared with beef insulin. Included among TCL reactive with pork insulin is one line (P2/9) that is autoreactive with human insulin. Antigen-presenting cells of known HLA type and monoclonal antibodies directed at class II major histocompatibility complex antigens were used to confirm the role of HLA-DR in restricting the response of insulin immune T cells. No preference or determinant selection within the donor's haplotypes was identified because either DR1 or DRw6 antigen-presenting cells could present the A loop of beef insulin. A TCL that recognized the A loop of beef insulin in association with DR1 was also alloreactive to HLA DR3, or a molecule closely linked to it, in the absence of insulin. A second T cell clone with insulin specificity and alloreactivity was also derived by allo stimulation of the donor's cells with DR3+ cells. When tested with a series of DR3+ stimulator cells, the alloreactivity was directed at diabetes-associated haplotypes. These data show that the T cell repertoire for insulin of a single diabetic donor encompasses that of multiple inbred animal strains and includes fine specificity for one to two amino acids, recognition of autologous insulin, and cross-reactivity with an allogeneic major histocompatibility complex antigen.