Variable Expression of Class I HLA Antigens on Platelets and T-lymphocytes : a Study of the Phenomenon and Its Mechanism

After reviewing the literature (1-83) , I concluded that: 1) the variable expression of class I HLA molecules is largely restricted to platelets and is not exhibited to the same extent by lymphocytes; 2) shed and secreted fonns of class I HLA molecules are present in plasma; and 3) an alternatively spliced class I HLA message lacking a transmembrane exon has been detected in peripheral blood mononuclear leukocytes. Based on these conclusions, I proposed the following hypotheses: 1. The expression of some class I HLA molecules varies to a much larger extent on platelets than on lymphocytes. 2. Alternative splicing of class I liLA messages with deletion of exon 5 pmduces secreted class I HLA molecules, and accounts for the variable expression of specific class I HLA molecules on platelets and the heterogeneity of plasma class I HLA. These hypotheses led to the following questions: 1. To what extent does the expression of HLA-B44 molecules vary on platelets and T-lymphocytes isolated from HLA-B44 heterozygous individuals? 2. How does the expression of HLA-B44 molecules compare to the expression of total class I HLA molecules on the platelets and T-lymphocytes isolated from HLA-B44 heterozygous individuals? 3. What are the relative ratios of full length versus alternatively spliced (lacking transmembrane exon) class I HLA messages in platelets and Tlymphocytes isolated from HLA-B44 heterozygous individuals and how does this correlate with cell surface expression of HLA-B44 on platelets and T-lymphocytes? The aims of my research studies were three-fold: 1. Characterization of HLA-B44 and total class I HLA expression on platelets and T-lymphocytes isolated from a panel of HLA-B44 heterozygous individuals. 2. Examination of the regulation of HLA-B44 expression on platelets and T-lymphocytes, by assaying these cells for the presence of a class I HLA mRNA encoding a transmembraneless form of the protein molecule. 3. Analysis of the relationships between class I HLA mRNA species found in platelets and \u27lymphocytes, and the cell surface expression of class I HLA alloantigens on these cells