Identification of T cells responding to a self-protein modified by an external agent

An interesting class of immune responses is that in which an environmental agent, modifies a self-protein. Heparin induced thrombocytopenia (HIT) is a ssociated with an antibody response in which the immunogen is a self-protei n, platelet factor 4 (PF4), modified by an external agent, heparin. We test ed the hypothesis that a T cell component exists in HIT, which like the hum oral response, also requires the combination of heparin and PF4 to be activ ated. We identify here, a subset of T cells derived from a subject with sev ere HIT, which were expanded preferentially in 14-day in vitro cultures spe cifically in the presence of PF4:heparin complexes. A combination of T cell receptor spectratyping, CDR3 sequencing, and clonotype-specific probe hybr idization were used to identify the responding T cells. The three BV17 T ce ll "clonotypes" thus identified had a CDR3 length of 10 amino acids, used B J1.2, and displayed a conserved CDR3 sequence motif. These T cells are an e xample of a cellular response to environmentally altered self and are likel y to be directly involved in HIT by functioning as T helper cells. The resu lts are discussed in terms of the possible role of modification of antigen presentation by the external agent in this response. (C) American Society f or Histocompatibility and Immunogenetics, 2001. Published by Elsevier Scien ce Inc.