Detergent-soluble HLA antigens contain a hydrophilic region at the COOH-terminus and a penultimate hydrophobic region.

Abstract

Purified, detergent-soluble HL-A antigens (p44,12) are composed of a glycoprotein of MW 44,000 (p44) and a peptide of MW 12,000 (p12), .beta.2-microglobulin. Upon digestion with papain p44,12 is converted to p39,12, then to p34,12, which retains antigenic activity. The NH2-terminal amino acid sequences of p34 and p44 are identical. Also, p44, p39 and p34 were purified, and comparison of their amino acid compositions showed that the COOH-terminal peptide removed by the 1st papain cleavage is hydrophilic and contains cysteine that can be alkylated after mild reduction. The penultimate COOH-terminal peptide removed by the 2nd papain cleavage is hydrophobic, and presumably anchors HL-A antigens to the membrane. This correlates with the observation that p44,12 and p39,12 bind detergent, while p34,12 does not. The orientation and integration of HL-A antigens in the lymphocyte membrane were thus defined, and the structure suggests that HL-A antigens span the plasma membrane.