V-1DTCR analysis on HIV recognition

With the development of crystal X-ray analysis, TCR-mediated recognition of epitopes presented by MHC antigens will soon to be revealed in terms of three-dimensional structure. Molecular and in vivo studies are needed to elucidate how T cells recognize highly variable HIV by using TCR, and how HIV evades TCR recognition. These studies, however, are yet to be conducted. We, therefore, began with establishing a method of studying TCR on a molecular level. We made a CTL clone which can recognize HIV-1 epitopes presented by both antigens, HLA-B*3501 and HLA-B*5101. The study revealed that the TCR of the CTL clone had 2 Va (Va 10.1, Va 12.1) and 1 Vb (Vb 5.6) (Eur. J. Immnol. 30:2521-2530, 2000). We then proceeded to the next step in which TCR was cloned from a CTL clone, followed by insertion of two sets of Va, Vbgenes (Va 10.1+Vb 5.6, Va 12.1+ Vb 5.6) into a murine retrovirus vector.

This study was to investigate whether these different HLA antigens were recognized either by different TCRs or by single TCR. And the study demonstrated TCR emergence on a cell infected with murine retrovirus encoded with both Va12.1and Vb5.6. They also showed that TCR recognized the epitopes presented by both HLA molecules and produced IL-2. This provided clear evidence that single TCR recognized epitopes presented by two different HLA molecules (J. Immunol. 169:4961-4963, 2002).

A very small number of groups have so far successfully established a method of identifying specificity of human TCR, by inducing TCR emergence on T cell. Our establishment of this method enabled us to study TCR recognition of HIV at the individual and molecular levels.