alleles of Mus musculus origin differed by only one 
or two coding and no silent nucleotide changes 
from the B2nf allele of inbred mice, it was a sur- 
prise that the B2m gene from Mus spretus differed 
by 14 nonsynonymous changes and only one silent 
change. This contrasts with the modest divergence 
seen in other members of the immunoglobulin 
superfamily. 
By comparison, the B2m genes of rats and mice 
differ by a similar number (14) of amino acid 
changes but a total of 52 nucleotide changes. In col- 
laboration with Dr. Jin-Xiong She (University of 
Florida, Gainesville), this observation has been con- 
firmed in five independent isolates of Mus spretus, 
which do not differ from each other, and extended 
to Mus spretoides, cervicolor, and spicilegus. The 
paucity of silent relative to coding changes suggests 
that diversifying selection accompanies speciation. 
The changes in the |82m molecule are concentrated 
on the face away from the MHC class I heavy chain, 
while the face that interacts with the a3 domain is 
conserved. 
Dr. Fischer Lindahl is also Professor of Microbi- 
ology and Biochemistry at the University of Texas 
Southwestern Medical Center at Dallas. 
Books and Chapters of Books 
Loveland, B.E., and Fischer Lindahl, K. 1991 . The 
definition and expression of minor histocompati- 
bility antigens. In Antigen Processing and Recog- 
nition (McCluskey, J., Ed.). Boca Raton, FL: CRC 
Press, pp 173-192. 
Wang, C.-R., Livingstone, A., Butcher, G.W., Her- 
mel, E., Howard, J.C., and Fischer Lindahl, K. 
1991. Antigen presentation by neoclassical MHC 
class I gene products in murine rodents. In Molec- 
ular Evolution of the Major Histocompatibility 
Complex (Klein, J., and Klein, D., Eds.). New 
York: Springer-Verlag, pp 441-462. (NATO ASI 
Series H, vol 59.) 
Articles 
Artzt, K., Barlow, D., Dove, W.F., Fischer Lindahl, 
K., Klein, J., Lyon, M.F., and Silver, L.M. 1991. 
Mouse chromosome 17. Mammalian Genome 
1:S280-S300. 
Attaya, M., Jameson, S., Martinez, C.K., Hermel, E., 
Aldrich, C, Forman, J., Fischer Lindahl, K., 
Bevan, M.J., and Monaco, J.J. 1992. Ham-2 
corrects the class I antigen-processing defect in 
RMA-S cells. Nature 355:647-649. 
Fischer Lindahl, K. 1 99 1 . His and hers recombina- 
tional hotspots. Trends Genet 7:215-216. 
Horton, R.M., Loveland, B.E., Parwani, A., Pease, 
L.R., and Fischer Lindahl, K. 1991 ■ Characteriza- 
tion of the spontaneous mutant H-2^^^'^ indi- 
cates that gene conversion in H-2 occurs at a 
higher frequency than detected by skin grafting./ 
Immunol 147:3180-3184. 
Koseki, H., Asano, H., Inaba, T., Miyashita, N., Mori- 
waki, K., Fischer Lindahl, K., Mizutani, Y., Imai, 
K., andTaniguchi, M. 1991- Dominant expression 
of a distinctive VI 4^ T-cell antigen receptor a 
chain in mice. Proc Natl Acad Sci USA 88:7518- 
7522. 
Pamer, E.G., Wang, C.-R., Flaherty, L., Fischer Lin- 
dahl, K., and Bevan, M.J. 1992. H-2M3 presents 
a Listeria monocytogenes peptide to cytotoxic T 
lymphocytes. Ce// 70:215-223. 
Silver, L.M., Artzt, K., Barlow, D., Fischer Lindahl, 
K., Lyon, M.F., Klein, J., and Snyder, L. 1992. 
Mouse chromosome 17. Mammalian Genome 
3:S24l-S260. 
TOLERANCE, AUTOIMMUNITY, AND THE MAJOR HISTOCOMPATIBILITY COMPLEX 
Richard A. Flavell, Ph.D., Investigator 
Tolerance, Inflammation, and Autoimmunity 
The relationship between immune tolerance and 
maintenance of an effective T cell repertoire is a 
balance that, when upset, can result in self-reactive 
lymphocytes and autoimmunity. What causes this 
breakdown of tolerance in autoimmunity is not un- 
derstood. Although central tolerance in the thymus 
eliminates most self-reactive T cells, extrathymic 
mechanisms also exist. In autoimmune diseases, tol- 
erance to peripheral antigens is lost and immune 
destruction of a specific cell type occurs, e.g., the 
islets of Langerhans in insulin-dependent diabetes 
mellitus (IDDM). 
Studies of tolerance have been facilitated by trans- 
genic mice expressing a tissue-specific antigen and 
by utilizing, as a source of T cells, transgenic mice 
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