02867nas a2200409   4500000000100000008004100001260001600042653002400058653002400082653003100106653001600137653001300153653002000166653001100186653001200197653002600209653003700235653002800272653002500300653003000325653004300355653002500398653000900423653003000432100001200462700001900474700001300493700001400506700001800520700001400538245005300552300001200605490000700617050001400624520180500638022001402443       1994                            d  c1994 Sep 2710aAmino Acid Sequence10aAntigens, Bacterial10aCD4-Positive T-Lymphocytes10aClone Cells10aEpitopes10aHLA-DR2 Antigen10aHumans10aleprosy10aLymphocyte Activation10aMajor Histocompatibility Complex10aMolecular Sequence Data10aMycobacterium leprae10apolymerase chain reaction10aReceptors, Antigen, T-Cell, alpha-beta10aRecombinant Proteins10aSkin10aT-Lymphocytes, Regulatory1 aMutis T1 aCornelisse Y E1 aDatema G1 aElsen P J1 aOttenhoff T H1 aVries R R00aDefinition of a human suppressor T-cell epitope.  a9456-600 v91  aMUTIS19943 a<p>The quality of the response produced by regulatory or helper T (Th) cells presently receives much attention because of its possible implications for vaccine development and immunomodulation. Apart from cytokines and so-called costimulatory signals, antigens and the presenting major histocompatibility complex (MHC) molecules may play a role in determining the type of T-cell response generated toward antigens. To examine the role of antigen and/or HLA in control of T-cell subset activation, we have studied a special case, namely CD4+ suppressor T (Ts) cells in leprosy. Mycobacterium leprae-induced Ts cell clones have been previously isolated from peripheral blood and skin lesions of lepromatous leprosy patients and were shown to specifically down-regulate mycobacterium-specific Th cell responses. Despite considerable effort, the antigens recognized by these Ts cells have thus far not been identified. Here we report that all HLA-DR2-restricted CD4+ Ts cell clones derived from a lepromatous leprosy patient recognize an epitope that maps between the amino acid residues 439 and 448 of the mycobacterial hsp65. The peptide was presented to these Ts cells by HLA-DRB1*1503, a recently discovered HLA-DR2 variant. Non-suppressor T-cell clones derived from the same patient recognized antigens other than the hsp65 and were also stimulated by other HLA-DR2 variants. In independent cloning experiments peptide 435-449 and recombinant hsp65 induced exclusively Ts cells in this lepromatous leprosy patient. The Ts clones recognizing this particular epitope were derived from at least seven different progenitors, as they expressed different T-cell receptor alpha and beta chains. Thus, our data indicate that a specific peptide-HLA class II combination may exclusively activate Ts cells.</p>  a0027-8424