In his textbooks and other writings, Klein introduced a new concept of immunology, in which he conceived the discipline as a branch of biological sciences, rather than as a narrow province of medical studies, as it had been represented traditionally.

He was the first to include in an immunology textbook sections emphasizing the importance of the so-called non-adaptive immune system (NAIS; he preferred to call it non-anticipatory).

Immunogenetics emerged in the 1930s as the study of genes controlling antigens (such as those of the various blood group systems) detected by antibodies.

In Klein's conception, immunogenetics was to deal with what immunology and genetics have in common—a set of genes that control and effect immune responses of any kind.

Earlier, Hugh O. McDevitt and his coworkers mapped an Immune response-1 (Ir-1) locus influencing the level of antibody production against the synthetic polypeptide (T,G)-L—A into the Mhc.

Klein and Donald C. Shreffler solved the problem by demonstrating that a given antigen could be present on molecules controlled by different loci.

These developments alerted immunologists on the one hand and transplantation biologists on the other of the Mhc’s potential importance for their respective disciplines.

In this manner, Klein contracted the H2 complex back to the version established by the serological methods, and propounded the view that the various responses (MLR, CML, etc.)

The generation is entirely random, so that receptors arise against all possible antigens, including those borne by the individual in which the differentiation takes place (the self-molecules).

The eliminated Tcrs might, however, by chance have had the capability of recognizing certain foreign antigens (nonself) in association with the nonresponder’ own Mhc molecules.

Inbred strains were, however, not suited for determining polymorphism, because assessing it required measuring gene frequencies in populations.

There were all sorts of problems associated with such an effort, most of which could, however, be alleviated by transferring a sample of H2 haplotypes from wild mice onto inbred (C57BL/10 or B10) background and thus producing a set of congenic B10.W lines.

These lines proved to be essential for the complete characterization of the new haplotypes; for the identification of natural intra-H2 recombinants; and for their use as a tool for mapping H2-associated traits.

Using a variety of methods, Klein and his colleagues were able to characterize H2 polymorphism in populations of wild mice from different parts of the world.

H2- typing of the global wild mice population revealed it to be fragmented into a large number of small subpopulations (demes), which differed in the presence and frequencies of alleles at the individual loci.

The reduction in chromosome number is due to centric fusion (Robertsonian translocation) of two telocentrics into a single metacentric.

Three features characterize the t region: suppression of recombination over the entire length of a complete t-haplotype; segregation distortion (t/+ males transmit the t-chromosome into more than 90 percent of their progeny); and frequent presence of homozygous lethal genes.

Klein group's combined t and H2 studies on wild mice from all over the world led to the identification and characterization of a number of new t-haplotypes.

Hence H2 polymorphism was expected to have arisen by an unusually high mutation (evolutionary) rate in the house mouse after its divergence from its nearest relative.

On the contrary, Klein and his co-workers found, by the methods then available, indistinguishable alleles in the two European house mouse species, Mus domesticus and M. musculus, which diverged from each other some 1–2 million years (my) ago.

Similarly large founding populations had to be postulated for the two lineages from which most of the hundreds of species inhabiting Lake Victoria in East Africa had diverged.

And even for Darwin's finches, widely believed to have arisen from a single pair of founders, Vincek and his colleagues came to the conclusion that the founding flock was at least 30 heads strong.

He crossed this bridge in a series of investigations into the nature of the speciation process in Darwin's finches and in haplochromine fishes of East Africa.

Klein and his associates studied both groups and using a variety of molecular markers contributed to the resolution of their phylogenetic relationships.

Contrary to earlier claims, Klein's group demonstrated that the species are not monophyletic and are by no means pauperized in their genetic polymorphism.

As in the case of the Ground finches of the Galapagos Islands, the haplochromine species of Lake Victoria are not distinguishable by any molecular markers Klein's group used in their studies.

In this case, Klein's group has demonstrated that increasing the number of genes in the input database does not improve the resolution power of the output phylogenetic trees.

They also contributed evidence for the omnipresence of Mhc genes in jawed vertebrates by identifying such genes in a wide range of species from bony fishes [zebrafish (Danio rerio), cichlid Aulonocara hansbaenschi, tilapia (Oreochromis niloticus), carp (Cyprinus carpio), guppy (Poecilia reticulata), threespine stickleback (Gasterosteus aculeatus), swordtail (Xiphophorus)]; through coelacanth (Latimeria chalumnae), African lungfish (Protopterus aethiopicus); birds [Bengalese finch (Lonchura striata), Darwin's finches and their South American relatives]; to metatherian mammals [red-necked wallaby (Macropus rufogriseus) and eutherian mammal [rodents such as the mole rat (Spalax ehrenbergi)] and a variety of primates including prosimians, New World monkeys (NWM, Platyrrhini), Old World monkeys (OWM, Catarrhini) and apes].

They also provided evidence that the selection leads to the independent, repeated emergence of similar or identical short sequence motifs by convergent evolution.

The hook-up seems to have arisen, when an identical short sequence motif arose by chance at both flanks of the initial C4-CYP21 doublet.