Heat shock protein Hsp60-reactive γ^δ cells: A large, diversified T-lymphocyte subset with highly focused specificity

Previously, we detected a subset of γδT cells in the newborn mouse thymus that responded to the mycobacterial heat shock protein Hsp60, as well as with what seemed to be a self-antigen. All of these cells expressed Vγ1, most often in association with Vδ6⁺. It was not clear, however, whether similar, mature γδ cells with Hsp60 reactivity are common outside of the thymus, or rather, whether they are largely eliminated during development. From the data presented here, we estimate that γδ cells responding to Hsp60 comprise 10-20% of normal splenic and lymph node γδ T cells. Such cells, derived from adult spleen, always express a Vγ1-Jγ4-Cγ4 γ chain, although not all cells with this γ chain show Hsp60 reactivity. Many of these Vγ1⁺ cells also express Vδ6-Jδ1-Cδ, though fewer than in Vγ1⁺ cells from the newborn thymus. Extensive diversity is evident in both the γ and δ chain junctional amino acids of the receptors of these cells, indicating that they may largely develop in the thymus of older animals or undergo peripheral expansion. Finally, we found that all such cells responding to both a putative self-antigen and to mycobacterial Hsp60 respond to a 17-amino acid synthetic peptide representing amino acids 180-196 of the Mycobacterium leprae Hsp60 sequence. This report demonstrates that a large subset of Hsp60-reactive peripheral lymphoid γδ T cells preexists in normal adult mice, all members of which respond to a single segment of this common heat shock protein.