837. CD1b tetramers bind alpha-beta T cell receptors to identify a mycobacterial glycolipid-reactive T cell repertoire in humans
Session: Oral Abstract Session: Innate and Adaptive Immunity to Infections
Saturday, October 22, 2011: 8:30 AM
Room: 156ABC

                                                                                                           

CD1b Tetramers Bind ab T cell Receptors to Identify

a Mycobacterial Glycolipid-reactive T Cell Repertoire in Humans

Anne G Kasmar MD MSc, Ildiko van Rhijn PhD, Tan-Yun Cheng PhD, Marie Turner MD, Chetan Seshadri MD, Andre Schiefner PhD, Ravi C Kalathur PhD, John W Annand MS, Annemieke de Jong PhD, John Shires PhD, Luis Leon PhD, Michael Brenner MD, Ian A Wilson PhD, John D. Altman PhD, and D Branch Moody MD 

Background: Mycolic acid containing glycolipids are abundant constituents of the mycobacterial cell wall which contribute to structure and virulence of the organism. Human T cells derived from mycobacterial lesions proliferate, secrete Th1 cytokines, and lyse target cells pulsed with mycolate antigens presented by CD1b in vitro.  Human CD1-restricted T cell responses can be detected during latent or active infection with Mycobacterium tuberculosis. Cumulatively, these data suggest that CD1-restricted T cells may contribute to human immunity to Mycobacterium tuberculosis.

Methods: In order to demonstrate CD1b-restricted, mycolate-specific T cells directly ex-vivo on a single cell basis, we developed CD1b tetramers which we used to identify mycolate-specific T cells in the peripheral blood of patients infected with Mycobacterium tuberculosis.

Results: CD1b-restricted T cells recognizing mycobacterial glycolipids are detectable in the circulation of humans infected with Mycobacterium tuberculosis using CD1b tetramers. The majority of these cells express CD4.

Conclusion: CD1b tetramers demonstrate a new CD4+ T cell population that recognizes a mycobacterial antigen; these newly identified cells may both contribute to anti-mycobacterial immunity and be subject to deletion during HIV infection.  


Subject Category: E. Innate and adaptive immunity to infections, including vaccine immunology

Anne Kasmar, MD MSc, Medicine/Infectious Diseases, Harvard Medical School, Boston, MA

Disclosures:

A. Kasmar, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.