Abstracts (complete list) - Wissenschaft Online

Cornelia Rosner, Lutz Walter
Functional analysis of MHC class I genes in the rhesus
monkey (Macaca mulatta)
The rhesus macaque represents a widely used animal model for the study of infectious
diseases, organ transplantation, and in development of vaccines. Recently, the major
histocompatibility complex (MHC) of the rhesus macaque (Mamu) was sequenced
completely (Daza-Vamenta et al., 2004), revealing extensive duplications in the class I
gene subregions. The sequenced haplotype displayed 2 and 19 loci, which show close
relationship to HLA-A and HLA-B, respectively. The functional significance of this
plethora of class I genes is, however, unknown so far.
In order to study the function of particular class I molecules, we cloned representatives
of Mamu-A and Mamu-B genes in an expression vector that contains AcGFP. These
constructs were transfected in the MHC class I-negative cell line K562. Surface staining
with the human MHC antibody W6/32 revealed variable expression patterns. Natural
killer (NK) cell activity against different Mamu-A and Mamu-B expressing transfectants
was tested by degranulation assays with freshly isolated rhesus monkey PBMCs. Some
transfectants exhibit higher inhibitory capacity, as exemplified by lower cell surface
expression of the CD107a molecule (degranulation marker). Currently, we are
investigating the specific binding of KIRs and MHC class I ligands by biochemical means.
Daza-Vamenta R, Glusman G, Rowen L, Guthrie B, Geraghty DE (2004) Genetic
divergence of the rhesus macaque major histocompatibility complex. Genome Res 14:
1501-1515