Human γδ+ T cells respond to mycobacterial heat-shock protein

Abstract

Most T cells recognize antigen through the T-cell antigen receptor (TCR)alpha beta-CD3 complex on the T-cell surface. A small percentage of T cells, however, do not express alpha beta but a second type of TCR complex designated gamma delta (ref. 2). Unlike alpha beta+ lymphocytes, gamma delta+ lymphocytes do not generally express CD4 or CD8 molecules, and the nature of antigen recognition by these cells is unknown. To study antigen recognition by gamma delta+ lymphocytes we raised a gamma delta+ alpha beta- -CD4-CD8- line from an individual immune to PPD (purified protein derivative). This line showed a specific proliferative response to PPD and to a recombinant mycobacterial heat-shock protein (HSP) of relative molecular mass 65,000 (65K). The gamma delta+ line was shown to exhibit a major response to HSP in the presence of autologous antigen-presenting cells (APCs). Minor responses occurred, however, with APCs matched for some HLA class I or II antigens, whereas no response occurred with HLA-mismatched APCs. These findings, therefore, document the requirement of HSP-reactive gamma delta+ lymphocytes for histocompatible APCs.

Depletion of γ/δ T cells does not prevent or ameliorate, but rather aggravates, rat adjuvant arthritis

“…Moreover, attempts to activate rat $8 T cells with mycobacterial antigens or heat-shock protein-treated cells, known to stimulate a subset of $ST cells in humans and mice (2,4,29), have so far been unsuccessful (Kuhnlein P, Hunig T: unpublished results). This indicates that there are probably substantial differences among species (15).…”

“…In humans (2) and mice (3), $8 T cells preferentially recognize mycobacterial antigens, such as heat-shock or stress proteins (4), and dominate the primary immune response to Mycobacterium tuberculosis (MT).…”

Limited heterogeneity of biased T‐cell receptor Vβ gene usage in lung but not blood T cells in active pulmonary sarcoidosis

“…37 Furthermore, expansion of g d + T cells in the peripheral blood of a subset of patients with sarcoidosis may be theoretically relevant because some g d + T cells respond to mycobacterial antigens. 38 The limited diversity in the T-cell repertoire at sites of granulomatous inflammation in sarcoidosis is also reminiscent of the restricted diversity found in the local tissue response to M. leprae in individuals with leprosy. 39,40 The fact that restricted diversity in the T-cell repertoire may be found in response to a complex mycobacterial organism lends credence to the speculation that one component of the T-cell response in sarcoidosis may be directed against an exogenous microbial antigen, perhaps cross-reactive to tissue antigens.…”

Takayasu Arteritis. Insights into Immunopathology.

“…Evidence has accumulated that γδ T-cells can recognize autologous HSPs and may play an important role in autoimmunity. 40,41) Because there was a significant increase in γδ T-cell infiltration, to clarify the mechanism of γδ T-cell infiltration, we examined the expression of HSP-65 in aortic tissue with Takayasu arteritis. HSP-65 was expressed weakly only in the media of aortic tissue from normal subjects, whereas the expression of HSP-65 was markedly increased in the media of aortic tissue with Takayasu arteritis.…”