Disruption ofepithelial y6T cellrepertoires bymutation ofthe Syktyrosine kinase (antigen receptor generearrangement/lymphocyte development/tissue compartmentalization/Rag2Syk chimeras)

Chimeric miceinwhichlymphocytes are deficient intheSyktyrosine kinase havebeencreated. Com- paredwithSyk-positive controls, micewithSyk-/-lym- phocytes display substantial depletion ofintraepithelial yaT cells intheskinandgut, withdevelopmental arrest occurring after antigen receptor generearrangement. Inthisdepen- dence onSyk, subsets ofintraepithelial y8Tcells aresimilar toBcells, butdistinct fromsplenic 'yS Tcells that develop and expand inSyk-deficient mice. Thecharacteristic associations ofcertain T-cell receptor V'y/V6 generearrangements with specific epithelia arealsodisrupted bySykdeficiency. Bcells andconventional a43Tcells compose twofunctionally distinct classes oflymphocytes. Whereas Bcells express anti- bodies thatrecognize native antigens, af3T cells recognize antigenic peptides presented bymajor histocompatibility