@article{open794, volume = {29}, number = {6}, month = {June}, author = {J N Agrewala and R J Wilkinson}, note = {Copyright of this article belongs to Wiley.}, title = {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.}, publisher = {Wiley}, year = {1999}, journal = {European journal of immunology}, pages = {1753--61}, keywords = {T lymphocyte, helper-inducer;Tuberculosis;Crystallin;Epitope, T lymphocyte;HLA-DR antigen}, url = {http://crdd.osdd.net/open/794/}, abstract = {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 {\ensuremath{<}} 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 {\ensuremath{<}} IC50 {\ensuremath{<}} 100 microM), affinity. These data support the hypothesis that the host MHC can influence CD4+ phenotype and have implications for subunit vaccination against tuberculosis.} }