Permissively recognized peptides which can activate lymphocytes are interesting diagnostic and vaccine candidates. In this study we have examined the influence of the presenting HLA-DR molecule on the phenotype of CD4+ T cells responding to the immunodominant peptide p91-110 of the 16 kDa protein of Mycobacterium tuberculosis.The 16 kDa antigen is predominantly expressed by Mycobacterium tuberculosis growing under oxygen deprivation and accounts for up to 25% total bacillary protein expression in these circumstances. Therefore, the 16-kDa protein may be an important antigenic target during bacillary latency. Eighteen CD4+ T clones specific for p91-110 were caractherized for the cytokine profile and analysized for the cDNA sequence of complementary determining regions (CDR3) of ?? TCR. All clones secreted IFN-? and were TCRBV2+ with a common CDR3 motif. The peptide p91-110 binds permissively to HLA-DR molecules and is recognized by Th clones when presented by homozygous Epstein-Barr virus-transformed B cell lines (L-BCL) bearing parental HLA class II molecules. Antibody blockade established that 16 out of 18 peptide-specific Th clones are DR restricted and two clones are DR-DQ and DR-DP restricted. Five out of 18 clones recognized p91-110 in association with both parental HLA-DR molecules and also with multiple diverse HLA-DR. Such T cells are known as unrestricted or promiscuous T cells. The functional advantage of promiscuous T cells recognizing antigen in association with more than one HLA molecule is they may expand preferentially and thus mount a rapid immune response against the pathogen. Further insight into the function of promiscuous T cells is therefore of particular interest for the development of peptide-based vaccines.
HLA-DR restricted T cell clones specific for an immunodominant epitope of the 16 kilodaltons antigen of Mycobacterium tuberculosis: Functional and molecular analysis
Di Sano C;
2001
Abstract
Permissively recognized peptides which can activate lymphocytes are interesting diagnostic and vaccine candidates. In this study we have examined the influence of the presenting HLA-DR molecule on the phenotype of CD4+ T cells responding to the immunodominant peptide p91-110 of the 16 kDa protein of Mycobacterium tuberculosis.The 16 kDa antigen is predominantly expressed by Mycobacterium tuberculosis growing under oxygen deprivation and accounts for up to 25% total bacillary protein expression in these circumstances. Therefore, the 16-kDa protein may be an important antigenic target during bacillary latency. Eighteen CD4+ T clones specific for p91-110 were caractherized for the cytokine profile and analysized for the cDNA sequence of complementary determining regions (CDR3) of ?? TCR. All clones secreted IFN-? and were TCRBV2+ with a common CDR3 motif. The peptide p91-110 binds permissively to HLA-DR molecules and is recognized by Th clones when presented by homozygous Epstein-Barr virus-transformed B cell lines (L-BCL) bearing parental HLA class II molecules. Antibody blockade established that 16 out of 18 peptide-specific Th clones are DR restricted and two clones are DR-DQ and DR-DP restricted. Five out of 18 clones recognized p91-110 in association with both parental HLA-DR molecules and also with multiple diverse HLA-DR. Such T cells are known as unrestricted or promiscuous T cells. The functional advantage of promiscuous T cells recognizing antigen in association with more than one HLA molecule is they may expand preferentially and thus mount a rapid immune response against the pathogen. Further insight into the function of promiscuous T cells is therefore of particular interest for the development of peptide-based vaccines.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
