TY - JOUR ID - open794 UR - http://crdd.osdd.net/open/794/ IS - 6 A1 - Agrewala, J N A1 - Wilkinson, R J N2 - T helper phenotype may be influenced by cytokine milieu, the differential expression of co-stimulatory molecules, antigen dose, and by differences in affinity at the TCR-peptide-MHC interface. We investigated the latter hypothesis by examining the response of six HLA-DR-restricted CD4+ T cell lines specific for the immunodominant and permissively recognized p91-110 epitope of the 16-kDa alpha-crystallin protein of Mycobacterium tuberculosis. Each line was generated from a sensitized HLA-DR-heterozygous donor and all proliferated when peptide was presented by autologous irradiated peripheral blood mononuclear cells. However, when HLA-DR-matched homozygous Epstein-Barr-virus-transformed B cell lines (L-BCL) were used as peptide-presenting cells there was heterogeneity in the response. The most pronounced proliferative response, and the highest IFN-gamma secretion and cytolytic activity was stimulated by L-BCL expressing molecules (DRB1*0101, *1501 and *0401) with high affinity (IC50 < 10 microM) for the 16p91-110 peptide. By comparison, IL-4 secretion or a lower proliferative response could occur when peptide was presented by alleles of high, or of intermediate (10 microM < IC50 < 100 microM), affinity. These data support the hypothesis that the host MHC can influence CD4+ phenotype and have implications for subunit vaccination against tuberculosis. VL - 29 TI - Influence of HLA-DR on the phenotype of CD4+ T lymphocytes specific for an epitope of the 16-kDa alpha-crystallin antigen of Mycobacterium tuberculosis. AV - restricted EP - 61 N1 - Copyright of this article belongs to Wiley. Y1 - 1999/06// PB - Wiley JF - European journal of immunology KW - T lymphocyte KW - helper-inducer;Tuberculosis;Crystallin;Epitope KW - T lymphocyte;HLA-DR antigen SN - 0014-2980 SP - 1753 ER -