The structure-function relationship of individual coding regions of class I mouse major histocompatibility complex proteins was studied by a combination of recombinant DNA, gene transfer techniques, and serologic and functional characterization. To examine the role of α1 and α2 regions in antibody and CTL recognition, the third exon of H-2D(d), K(d), and L(d) transplantation antigen genes was replaced by the homologous coding region of the Qα-2-coded class I gene, Q6. We have chosen to carry out the exon shuffling experiments between these two different types of class I genes, because they are structurally similar and did not evolve to carry out identical functions. Therefore, it is less likely that the hybrid proteins well fortuitously recreate α1-α2 controlled functionally important determinants. The replacement of H-2 α2 coding region with its Q6 counterpart had different effects on the expression of the three genes. The mutant H-2D(d) gene transfected into L cells was expressed at high levels and retained several of the serologic determinants found on parental H-2D(d) and Q6 domains. The serologic epitopes on the mutant H-2K(d)-transfected cells were detectable at very low levels, whereas the product of the mutant H-2L(d) gene could not be identified at all. Analysis of cells transfected with mutant H-2D(d) gene with alloreactive and minor antigen(s)-restricted cytotoxic T cells indicated that the hybrid proteins lost the ability to be recognized by T cells. Our data suggest that cytotoxic T cells recognize conformational determinants composed of amino acids from α1 and α2 regions. Alternatively, it could be proposed that T cell recognition sites located in a single α1 or α2 protein region are susceptible to distortion upon α1-α2 interactions. Such susceptibility to conformational changes of the amino-terminal domain of transplantation antigens could be of functional importance for H-2-restricted antigen presentation.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Immunology|
|State||Published - Dec 1 1985|
ASJC Scopus subject areas
- Immunology and Allergy