David A. Lawlor

A transposable epitope of HLA-137, B40 molecules

The monoclonal antibody M1340.2 defines a novel subtype of HLA-1340 that is expressed by the Sweig cell line. This molecule, called HLA-B40*, lacks an antigenic determinant that is common to HLA-137 and the HLA-Bw60 subtype of HLA-1340. Genes encoding HLA-B40* and HLA-BW60 have now been isolated and the amino acid sequences of these proteins compared with other HLA-13 locus molecules. These results show that HLA-B40* is a unique protein which differs from HLA-BW60 by eight amino acid substitutions. Comparison of the sequences for HLA-B40*, -Bw60, and -B7 localizes the MB40.2 epitope to a cluster of three substitutions at positions 177, 178, and 180 at the end of the α2 domain. Gene conversion or reciprocal recombination are postulated to have transferred this cluster of substitutions, and their associated epitope, during the evolution of HLA-B locus genes. The epitope may consist of an a helical segment which is exclusively found on MB40.2-positive molecules.

DNA Analysis of the Windover Population

The discovery that a water-saturated environment can preserve DNA in tissue has provided a significant additional source of genetic material for the rapidly expanding field of ancient DNA (aDNA) analysis. In this chapter we describe some results of our genetic study of the Windover archaeological site. Windover is presently the most extensively characterized wet site with regard to ancient human DNA. Our intent is to describe the conditions of DNA preservation, discuss reasons for the surprisingly good state of that preservation, and outline the current status of genetic reconstruction of this 7.000–8,000-year-old population. Throughout, we have also attempted to highlight elements of our Windover study which may serve as useful predictive and methodological guides for retrieval and analysis of aDNA from other wet sites.

Structure of CD8 alpha and beta chains of the orangutan: novel patterns of mRNA splicing encoding hingeless polypeptides.

Class I major histocompatibility complex (MHC) molecules present peptide antigens to the antigen receptors of CD8 positive T cells. They are made up of two pairs of domains which are structurally and functionally distinct (Bjorkman et al. 1987a, b). The c~ 1 and c~ 2 domains of the heavy chain pair to form the characteristic antigen-recognition site that binds peptide and interacts with the T-cell receptor. The other two domains, % of the heavy chain and/32-microglobulin (/32-m), have structures very similar to that of the CH3 immunoglobulin heavy chain domain (Becker and Reeke 1985; Bjorkman et al. 1987a). One of these immunoglobulin-like domains, %, has been shown to contribute to interactions with the CD8 coreceptor of T cells. In particular an acidic exposed loop formed by residues 221-229 of c~ 3 is implicated in the formation of a binding site for the CD8 c~ chain (Conholly et al. 1990; Salter et al. 1990). The involvement of /32-m in CD8 interactions has yet to be assessed. In humans, the class I MHC heavy chain genes (HLAA, B) are noted for their polymorphism (Bjorkman and Parham 1990) whereas genes encoding CD8 c~ and /3 chains appear monomorphic (Littman 1987; Parnes 1989). For HLA-B there is almost no polymorphism in the % domain, contrasting with HLA-A where it is significant (Parham et al. 1989) and which in one case is known to affect both interaction with CD8 and T-cell function (Salter et al. 1989). Further modulation of the class I MHC-CD8 interaction may come from the use of differentially spliced forms of the CD8 c~ and /3 chain

How Similar Are Chimpanzee and Human Class I Antigens

Although the HLA and H-2 systems have provided considerable information of the structure and function of the class I MHC molecules, little is known concerning the evolution of the genes during the process of mammalian radiation. This is largely due to the fact that the two best studied species (mouse and man) diverged 75 to 90 million years ago. Comparison of nucleotide sequences has suggested that some of the current HLA-A,B,C alleles are of relatively ancient origin; however, sequence information with species closely related to man has been lacking. To investigate the possibility that HLA alleles predate primate speciation, our efforts are directed towards analyzing the class I molecules of the chimpanzee, a species with which we shared an ancestor some 3.5 to 5 million years ago.