Genetic recombination has been proposed to have played a major role in
generating the extensive polymorphism that distinguishes the genes of
the major histocompatibility complex (MHC). The proximal region of th
e murine H-2 represents a unique segment of DNA encompassing at least
four hotspots for meiotic recombination. One of these hotspots lies wi
thin the second intron of the class II Eb gene and has been defined at
the nucleotide level for a number of simple two-allele crosses. In th
is report we studied two crosses in which one or both parents in thems
elves were H2Eb recombinants and three alleles were present within the
hotspots of each pair of the parental haplotypes. Nucleotide analysis
indicated that the break points in these secondary recombinants, like
those in the primary recombinants, were also discrete and clustered w
ithin the H2Eb second intron. Thus, in one instance two and in the oth
er instance three alleles were present within the hotspots of these re
combinants. These observations strongly suggest that meiotic recombina
tion could be an important mechanism contributing to MHC polymorphism.