For the last several years, our laboratory has been concerned with the biochemistry and genetics of the class I antigens of the major histocompatibility complex of the mouse. We have found that beta-2 microglobulin displays genetic structural polymorphism, which has made it possible to map the B2m locus to the H-3 region of chromosome 2. We have been involved in a long-term program using biochemical techniques to study the genetics of the Qa-Tla region of the MHC. These studies are beginning to provide an understanding of the unusual immunogenetic features of this region, particularly the anomalous expression of Qa and TL antigens on leukemias. We have found that the Tla region genotype (chromosome 17) influences the quantity of B2M (coded by chromosome 2); measurement of B2M messenger RNA levels indicates that this control is exerted at the transcriptional level. We have used molecular biological criteria to detect genetic polymorphism of a novel chromosome 17 gene, an alpha-hemoglobin pseudogene, and demonstrated that it is closely linked to the distal side of the H-2K locus. We intend to continue these studies by carrying out experiments on the biochemical genetics of class I antigens, including molecular-biological techniques, with special emphasis on control of B2m expression by the Tla region, dissection of the complexity of the Qa-Tla region gene products, and analysis of the nature of the expression of the Qa-Tla region gene products on leukemias and normal cells. (LB)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037374-04
Application #
3175229
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1983-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Immune Disease Institute, Inc.
Department
Type
DUNS #
115524410
City
Boston
State
MA
Country
United States
Zip Code
02115
Michaelson, J (1993) Cellular selection in the genesis of multicellular organization. Lab Invest 69:136-51
Salant, E; Michaelson, J (1990) TL.8, a new antigenic determinant of the TL system. Immunogenetics 31:410-1
Whitehead, A S; Rits, M; Michaelson, J (1988) Molecular genetics of mouse serum amyloid P component (SAP): cloning and gene mapping. Immunogenetics 28:388-90
Perkins, D L; Michaelson, J; Marshak-Rothstein, A (1987) The lpr gene is associated with resistance to engraftment by lymphoid but not erythroid stem cells from normal mice. J Immunol 138:466-9
Michaelson, J; Boyse, E A; Ciccia, L et al. (1986) Biochemical genetics of TL antigens. Immunogenetics 24:103-14