| Citation | Peter Parham is distinguished for defining the molecular basis and functional effects of polymorphisms of human major histocompatibility complex ( HLA ) class 1 molecules and their killer cell immunoglobin-like receptors ( KIR ). These polymorphisms diversify immune systems, reducing the vulnerability of populations to epidemic infection. Parham made monoclonal antibodies against HLA polymorphism and pioneered their application to the study of HLA. From structural analysis of HLA class 1 alleles he established the principles by which HLA class 1 genes evolve through inter-allelic conversion and change their immunological functions. Parham discovered a polymorphism that affected CD8 binding and went on to map out the CD8 binding site on the HLA class 1 molecule. From comparison of ethnic groups he discovered an extraordinary diversity of 'new' HLA-B alleles in South American Indians, distinguishing them from other populations. In aggregate the results of Parham's analyses both required and made possible the replacement of serological HLA typing with more precise methods based on nucleotide sequence. Parham showed that the human killer cell immmunoglobulin-like receptors are encoded by a diverse and polymorphic gene family. He found that this diversity creates NK-cell repertoire within each person, differences in repertoire between persons and ethnics groups, and is largely species specific. The development of the NK cell repertoire was shown to involve both the KIR genes and the HLA genes. Parham's work on HLA class 1 polymorphism is routinely described in immunology text books; his pioneering studies on human KIR repertoire and diversity opened up a new field of KIR immunogenrtics in which disease susceptibilities and clinical outcomes of transplantation are being correlated with KIR type and difference. |