Unambiguous HLA Typing for Studies of Human Immunity (35.18)

Abstract

Abstract The Major Histocompatibility Complex (MHC) is recognized as the most polymorphic region of the human genome. Our HLA typing laboratory at the University of Oklahoma Health Sciences Center has performed more than 30,000 HLA typings in the past 10 years. We have systematically overcome various capacity and cost constraints to provide precision, DNA sequence-based, HLA typing data for studies of transplantation, vaccine development, and autoimmunity. A confounding variable in the HLA typing field is data heterogeneity; different HLA laboratories provide different levels of resolution when reporting an HLA type for autoimmune, transplant, and vaccine studies. For example, HLA-A*02, A*0201, or A*0201/09/43N/66/75/83N/89/97 might all be reported for a like sample. Such data heterogeneity hinders data integration and comparison. On the basis of our experience with HLA typing and with functional assays such as the ELISpot and tetramer staining, we propose a system of HLA typing that encompasses known functional regions of the HLA molecule. The DNA sequencing of the appropriate exons at various HLA loci, along with the resolution of known null substitutions, will provide cost efficient HLA typing data that can be integrated among different laboratories. Improved HLA data uniformity will ultimately strengthen studies of human immune responses and disease.