Nature 247, 457 - 461 (15 February 1974); doi:10.1038/247457a0

Subcellular Separation and Molecular Nature of Human Histocompatibility Antigens (HL-A)

D. SNARY^*, P. GOODFELLOW^†, M. J. HAYMAN^‡, W. F. BODMER^§ & M. J. CRUMPTON

^*National Institute for Medical Research, Mill Hill, London NW7 1AA
^†Genetics Laboratory, Department of Biochemistry, University of Oxford, Oxford
^‡National Institute for Medical Research, Mill Hill, London NW7 1AA
^§Genetics Laboratory, Department of Biochemistry, University of Oxford, Oxford
National Institute for Medical Research, Mill Hill, London NW7 1AA

HISTOCOMPATIBILITY antigens have been solubilised by various means¹, especially proteolytic digestion²⁻⁴, sonication⁵ and extraction with 3 M KCl⁶ or detergents⁷⁻⁸. Although detergents seem to solubilise the intact antigens these preparations have, until recently, proved difficult to fractionate further, whereas the products of the other procedures have proved amenable to purification but probably represent fragments of the membrane-bound antigen. This interpretation is based on the following arguments. First, solubilisation with 3 M KCl seems to depend on the presence of cell sap and was markedly reduced by protease inhibitors⁹. Second, in contrast to the detergent-solubilised antigen¹⁰, the other procedures yield non-aggregated products which, in general, possess similar molecular weights within the range 35,000−55,000¹⁰⁻¹². Third, mouse and human histocompatibility antigens obtained by papain digestion seem to be glycoproteins (3−8% carbohydrate), whereas the antigens solubilised from guinea pig and human tissues by sonication and 3 M KCl extraction have been reported to be non-glycosylated (less than 1 % carbohydrate)¹². This dichotomy would be explicable if the latter procedures had caused degradation and the consequent separation of the carbohydrate from the molecule bearing the antigenic determinant.

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