The most significant finding has been the discovery that the Ly-17 alloantigen is identical with the FcGamma2b receptor (FcR). As previous genetic evidence had inseparably linked the Ly-17 gene to the Mls locus on chromosome 1 we now postulate that FcR serves as the long-sought Mls product. Whereas a number of longstanding observations are in support of this hypothesis, the most notable experimental fact is the ability of Fc fragments to activate T helper (TH) cells. We propose to produce further evidence that Ly-17 serves as the Mls product. Ly-17 antigen will be purified and characterized biochemically. Peptide and amino acid sequence analyses will be performed. Ly-17 will be implanted via fusogenic liposomes in suitable antigen-presenting cells (APC) to test whether this maneuver will confer transient Mls stimulatory capacity. The potentially important spatial association of Ly-17 and Ia reported earlier will be re-evaluated. Finally, we will investigate the mechanism of Mls activation. Two models are suggested. The first assumes that a positive signal, emanating from Ly-17 (FcR) to an unidentified acceptor A, is enhanced in the Mls-mismatched APC-TH pair, leading in synergy with the autoreactive Ia-Ti interaction to TH activation (""""""""heteroclicity"""""""" model). In the second model the opposite assumption is made that Ly-17 (FcR) normally imparts a dampening signal to TH. In the Mls mismatched APC-TH pair this signal may not function properly, allowing TH activation through auto-MLR (""""""""decontrol of autoreactivity"""""""" model).
| Hammerling, U; Toulon, M; Chun, M et al. (1988) Bidirectionality of mixed lymphocyte stimulation (Mls) response. Effects of Mlsb stimulator cells on Mlsa helper cells. J Immunol 140:2543-8 |
| Hammerling, U; Toulon, M; Palfree, R G et al. (1988) Mls and the helper T-cell repertoire. I. Mls as a regulator of T-helper cell activation. J Immunogenet 15:169-74 |
| Hoffmann, M K; Chun, M; Dennig, D et al. (1988) Mls and the helper T-cell repertoire: II. Does the Mls gene product influence the formation of the T-cell repertoire? Studies with Mls tolerance. J Immunogenet 15:175-81 |
| Holmes, K L; Palfree, R G; Hammerling, U et al. (1985) Alleles of the Ly-17 alloantigen define polymorphisms of the murine IgG Fc receptor. Proc Natl Acad Sci U S A 82:7706-10 |
| Mark, W H; Kimura, S; Hammerling, U (1985) Biochemical characterization of murine lymphoid alloantigen Ly-m20.2, a cell surface marker controlled by a gene linked to the Mls locus. J Immunol 135:2635-41 |
