T-CELLS BEARING V-BETA-6 T-CELL RECEPTORS IN THE CELL-MEDIATED IMMUNE-RESPONSE TO MYCOBACTERIUM-LEPRAE

The skin lesions of leprosy provide a window into the immunoregulatory events involved in the human immune response to infection. T cells ar e thought to play a vital role in the pathogenesis of different forms of the disease. To identify predominant specific T cell subpopulations in leprosy lesions, the TCR-beta chain repertoire was simultaneously studied in skin biopsy specimens and PBMC from both immunologically re sistant tuberculoid leprosy and susceptible lepromatous leprosy patien ts. This was accomplished by obtaining RNA from lesions and PBMC, synt hesizing cDNA, and performing the polymerase chain reaction. We found that TCR gene subfamilies Vbeta6.1 through Vbeta6.4 (Vbeta6.1-4) were strikingly overrepresented in lesions vs PBMC of seven of nine tubercu loid patients but only one of nine lepromatous patients. Similarly, Vb eta6.5/6.8/6.9 subfamilies were predominant in four of nine tuberculoi d patients, but none of the nine lepromatous patients. To explore the influence of the complementarity-determining region 3 (CDR3) in select ion of T cells expressing Vbeta6 TCR, we sequenced the Vbeta6.1-4-Cbet a polymerase chain reaction products derived from the lesions and PBMC of two tuberculoid patients. From the analysis of deduced amino acid sequences, we found conserved amino acid residues and amino acid motif s in the CDR3 region of the lesion-derived sequences from each patient . Our data suggest that the nominal Ag select T cells bearing Vbeta6 T CR in the cell-mediated immune response to Mycobacterium leprae.