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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.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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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.
 
Creator Agrewala, J N
Wilkinson, R J
 
Subject QR180 Immunology
 
Description 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.
 
Publisher Wiley
 
Date 1999-06
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/794/1/agrewala1999.pdf
Agrewala, J N and Wilkinson, R J (1999) 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. European journal of immunology, 29 (6). pp. 1753-61. ISSN 0014-2980
 
Relation http://crdd.osdd.net/open/794/