The H-2 model for the major histocompatibility systems.

Thirty-five years ago, Gorer (1936), working with inbred strains of mice, discovered four blood group antigens and showed (Gorer 1937) that one of them, antigen II, was also present in fixed tissues and played a decisive role in determining susceptibility or resistance to tumor transplants. Following the suggestion of Snell (1948) that antigens concerned in transplantation reactions should be called histocompatibility (H) antigens, the designation antigen II was changed to H-2. The gene controlling the H-2 antigen was shown to be linked with Fused (a gene for a tail anomaly) in the 9th linkage group (Gorer et cd. 1948). It soon became apparent through histogenetical studies by Snell and his coworkers (for a review, see Snell 1953) that what looked at first like a simple biaJlelic locus was actually a multiallelic system with many different H-2 alleles present in different inbred strains. At the same time, serological studies by Gorer, Amos, Hoecker, and others (for a review, see Gorer 1959) revealed that the H-2 antigen was not simple, but consisted of increasing numbers of antigenic components. In 1951, Snell showed that Fl hybrids between inbred strains BALB/c {H-2^) and CBA {H-2^) were susceptible to an A strain tumor and suggested that the H-2^ allele of strain A was actually composed of two components, d and k, and should be therefore written as H-2^^, This was the first indication of a bipartite structure of the H~2 locus. The bipartity was further supported by detection of crossingover between the d and k components (Allen 1955), but was later obscured by discoveries of additional recombinants and an increasing serological complexity. The idea re-emerged in 1965 when it was discovered that the Ss (serum protein) locus was located within the complex chromosomal region controlling H-2 antigens (Shreffler 1965).