ABSTRACT
HY was not the first minor histocompatibility (H ) antigen to be detected in mice, since the work of several investigators during the first half of the 20th century had previously established that there were a number of independently segregating loci controlling the rejection of allogeneic skin and tum or grafts in mice (reviewed in ref. 1). One of these, George Snell, was therefore well placed to interpret the findings of Eichwald and his colleagues when they reported in 1955 that in some but not all inbred strains of mice, females could reject skin grafts from males of the same strain.2 Snell pointed out that these results were consistent with there being a m inor H locus on the Y chrom osom e.3 Subsequently, Billingham and his colleagues used HY as a model ‘weak’ transplantation antigen to further explore the induction of neonatal tolerance,4,5 following the pioneering work in Peter M edawar’s laboratory on neonatal tolerance to incompatibilities at H 2, the major histocompatibility complex (M H C).6'8 Exploration of the genetic control of the ability to reject syngeneic male grafts was undertaken by Bailey, another pioneer of minor H antigens: he extended the analysis of HY responder and non-responder strains and showed that a gene within the M HC was the major controlling factor.9,10
Investigation of minor H antigens was limited to in vivo responses until the 1970s: at the beginning of that decade attempts were made to extend the analysis by making male specific antibodies, and whilst these initially looked promising,11 the results were difficult to repeat in other laboratories because of the low titers of the antibodies, and from studies typing individuals with abnormal Y chromosomes it appeared that the determinant identified serologically (renamed SDM) was not the same as the minor histocompatibility antigen, HY, detected by T cells.12
