Edith Zeller

The biologic significance of HL-A antigen markers in myasthenia gravis.

dermatitis herpetiformis,27-29 Hodgkin’s disease,30. 31 systemic lupus erythematosus with skin manifestation,32 juvenile diabetes,33 Grave’s disease 34 and idiopathic Addison’s disease.35 In myasthenia gravis (MG) we are aware of reports from six different laboratories indicating an increase in frequency of HL-A8 (FIGURE 1) .36-42 Our initial observations also suggested a relation between HL-A8 and thymic morphology in MG.40 Although some skepticism about the significance of HL-A in association with disease may be rai~ed,4~ studies of inbred rodents support the contention that genes associated with the major histocompatibility systems control immune responses to a variety of bacterial and other antigens.2-6 Genetic factors predisposing to autoimmune thyroiditis 4 4 t 45 and lymphocytic choriomeningitis 46 have been linked to the major histocompatibility systems. Since abnormal HL-A distribution often has been observed in diseases of possible autoimmune origin, the existence of immune response genes with linkage to the HL-A system has been We report here the results of HL-A typing in our current series of 71 Caucasian MG patients. 23

Major histocompatibility complex class I genes of Peromyscus leucopus

Class I genes of the Peromyscus leucopus major histocompatibility complex (MhcPele) were examined by Southern blot hybridization, genomic cloning, and DNA sequencing. At least three distinct subtypes of Pele class I genes were discerned, which we have designated Pele-A, B, and C. The nucleotide sequences of exon 5-containing regions (encoding the transmembrane domain) suggested that Pele-A genes are homologs of mouse H-2K, D, L, and Q genes and that Pele-B genes correspond to mouse Tla genes. The Pele-C genes appeared similar to mouse M1 genes. The number of unique genes in each subtype cloned from an individual P. leucopus were 20 for Pele-A, 13 for Pele-B, and 2 for Pele-C. Three genomic clones showed cross-hybridization to both Pele-A and Pele-B gene-specific probes. Six genomic clones remained unclassified as they did not cross-hybridize to exon 5-containing probes from Pele-A, B, or C genes. The homology between the transmembrane domains of Pele class I gene subtypes was found to be similar to that observed between the transmembrane domains of H-2 subtypes (or groups). Interspecific similarity of exon 5 was found to be 81%–88% between Pele class I genes and their H-2 counterparts.

Strong HLA-DR expression in T cell cultures after activation is necessary for IL-2-dependent proliferation

We have examined the appearance of DR antigens on human T cells activated by PHA, using a monoclonal anti-DR framework antibody and a large panel of human HLA typing sera. Strong DR expression within the culture by day 8 was associated with the ability of cells to grow for long periods in IL-2 containing medium, whereas weak or absent DR expression was predictive of poor in vitro growth. All the cells responded equivalently to initial stimulation with PHA. These data support the hypothesis proposed by Moretta et al. to explain blocking of IL-2-dependent proliferation by an anti-DR antibody--that DR molecules may be involved in the transmission of signals by IL-2.

Polymorphism in the major histocompatibility complex class II genes of Peromyscus leucopus.

The fifty or more species of Peromyscus (family Cricetidae, subfamily Cricetinae) may be the most ubiquitous rodents in North American habitats (Baker 1968). DNA-DNA hybridization studies (Bowden 1983) suggest that Cricetidae and Muridae families split 40-60 million years ago. Mus and Rattus by comparison are more related, having diverged approximately 20 million years ago.Though representatives of the genus Peromyscus were used experimentally as early as the late nineteenth century, nothing is known of the Peromyscus major histocompatibility complex (MHC). Evolutionary relationships between the MHCs of several species may prove valuable in understanding the biology of the MHC which remains obscure despite a strong immunological foundation. Besides MHC evolutionary implications, our interest specifically in the Peromyscus leucopus MHC comes from the observations that this species has twice the lifespan of Mus and Rattus (Sacher and Hart 1978, Smith et al. 1989) and that in mice the MHC has been shown to influence the rate of aging and maximum lifespan (Smith and Walford 1977, Walford 1987). Furthermore, studies have suggested that, besides immune function, genes within or linked to the MHC may influence DNA repair (Walford 1987), levels of mixed function oxidases (Koizumi et al. 1987), and reproductive senescence (Lerner et al. 1988). For these reasons it seems reasonable to investigate age-related function in Mus harboring MHC genes from Peromyscus. To this end, we are creating inbred Peromyscus strains and defining the MHC at the molecular level. As a first step in analyzing the MHC of Peromyscus, we examined the number and degree of polymorphism of MHC class II genes by observing restriction fragment length polymorphisms (RFLPs) in partially inbred lines of P. leucopus. We established a colony of P. leucopus in 1981 with 20 breeding pairs obtained from the Argonne

The “Thompson” Specificity and the HL-A Human Leukocyte System

Summary Population and family studies of the Thompson specificity and four factors of the first sublocus of the HL-A main human leukocyte system are described. The Thompson specificity is strongly allelic or pseudoallelic to the other factors of the sublocus. At the same time, evidence of crossover between Thompson and HL-A has been found in 3 of 7 families studied to date. Taken together, population and family data suggest the possibility that the Thompson factor is the expression of gene interaction or epistasis involving the HL-A and some other system.