Defining HLA-A locus alleles from DNA using ARMS-PCR.

The HLA system is a highly polymorphic group of genes which play a central role in the immune response. The definition of the HLA system makes an important contribution to a number of fields. In the clinical setting it is a requirement for transplantation. For anthropology, the HLA system is a useful marker for assessing population groups. Functionally, it is an important component of the T cell mediated immune response. The definition offered by the established method of serology to HLA class I tissue-typing is restrictive since serology fails to discriminate between alleles which are functionally distinct. This research represents one of the first DNA based approaches and the first by PCR-SSP, to define HLA class I specificities, with particularly reference to the HLA-A locus. This thesis charts both the development and application of a robust, simple to perform, easy to interpret yet highly powerful PCR based system in which allelic definition is demonstrated. In addition to resolution, a DNA approach offers many practical advantages over the restrictive demands of a serological typing. Further more, this thesis examines the functional aspect of polymorphism, in defining the peptide binding preferences of a group of closely related HLA specificities. By so doing, this thesis shows the relevance of a highly definitive approach to HLA typing