SELECTIVE USAGE OF DEFINED TCRBV GENES IN RESPONSE TO FILARIAL ANTIGENS

The characterization of T cell reactivities that are prone to down-mod ulation by filarial parasites is central to understanding how these ne matodes can survive for long periods of time within their human host a nd to design appropriate immunoprophylactic measures, In the present s tudy, TCRBV gene usage was analyzed in response to filarial antigens b y PCR using a panel of TCRBV gene segment family-specific oligonucleot ide primers, Analysis of individuals highly responsive to Brugia malay i adult worm antigen (BmA) (n = 4) indicated that following stimulatio n with BmA a maximum of four TCRBV gene families were over-represented in each subject. Those were TCRBV2, 9, 19 and 23 in subject 1; TCRBV8 , 9 and 16 in subject 2; TCRBV2, 8, 9 and 11 in subject 3; and TCRBV13 and 23 in subject 4, The analysis of one subject who was unresponsive to BmA before but regained responsiveness after diethylcarbamazine tr eatment revealed that there was no. overexpression of a particular TCR BV gene family before chemotherapy, whereas after chemotherapy three T CRBV gene families (TCRBV8, 16 and 19) were found to be overexpressed. Complementarity determining region 3 size analysis of a selection of the overexpressed TCRBV genes displayed oligoclonality in some of the observed expansions, Together these observations show that limited T c ell subpopulations are clonally amplified in BmA-stimulated peripheral blood mononuclear cells of filarial responder subjects, possibly driv en by a restricted number of antigens.