Search for the antigen presenting element for human Vγ2Vδ2 T cells

In humans, γδ T cells are a unique subset of peripheral blood CD3+ T cells of which Vγ2Vδ2 T cells form the major subset (50-95%). During microbial infections, Vγ2Vδ2 T cells recognize small, nonpeptide prenyl-pyrophosphate antigens such as HMBPP that are essential microbial metabolites and expand to numbers as high as 50% of total T cell numbers. The recognition of non-peptide antigens by Vγ2Vδ2 T cells is TCR mediated. The existence of an antigen presenting molecule for nonpeptide antigens is suggested by the requirement for T cell contact with the APC, by the lack of antigen binding to the Vγ2Vδ2 TCR, and by our finding that TCR mutations in CDRs distant from the putative antigen binding site abrogate recognition. However, identification of the putative antigen presenting molecule has been hindered by the inability to achieve stable association of nonpeptide antigens with the APC surface. In our lab, we are employing a combinatorial approach of using 1) chemical crosslinking b) expression library cloning and c) biochemincal methodology to identify the putative antigen presenting element for Vγ2Vδ2 T cells. The results so far suggest that nonpeptide antigens are presented by a novel antigen presenting molecule that is widely distributed, non-polymorphic, and not classical MHC class I, class II, or CD1.

Wang H, Sarikonda G, Puan KJ, Tanaka Y, Feng J, Giner JL, Cao R, Mönkkönen J, Oldfield E, Morita CT. Indirect stimulation of human Vγ2Vδ2 T cells through alterations in isoprenoid metabolism. J Immunol. 2011 Nov 15;187(10):5099-113. Epub 2011 Oct 19. PubMed PMID: 22013129.

Sarikonda G, Wang H, Puan KJ, Liu XH, Lee HK, Song Y, Distefano MD, Oldfield E, Prestwich GD, Morita CT. Photoaffinity antigens for human gammadelta T cells. J Immunol. 2008 Dec 1;181(11):7738-50. PubMed PMID: 19017963; PubMed Central PMCID: PMC2696061.

Puan KJ, Jin C, Wang H, Sarikonda G, Raker AM, Lee HK, Samuelson MI, Märker-Hermann E, Pasa-Tolic L, Nieves E, Giner JL, Kuzuyama T, Morita CT. Preferential recognition of a microbial metabolite by human Vgamma2Vdelta2 T cells. Int Immunol. 2007 May;19(5):657-73. Epub 2007 Apr 19. PubMed PMID:17446209.

Morita CT, Jin C, Sarikonda G, Wang H. Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. Immunol Rev. 2007 Feb;215:59-76. Review. PubMed PMID: 17291279.