Ertl, H.

Koszinowski, Ulrich H.

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©          Nature Publishing Group1975sso baboons that I could see at the time were not unduly alarmed at my presence once they had reached the top of the cliff. MARTIN PICKFORD Department 0/ Geology, Queen Mary College, University 0/ London, Mile End Road, London EI 4NS, UK 1 Hamilton, W.J.,Buskirk,R.E., andBuskirk, W. H., Nature, 256, 488 (1975). H-2 antigen rt'striction of viral infection KOSZINOWSKI and Erd demonstrated1 that T lymphocytes immunised in vivo against virus kill virus-infected target cells only when these share H-2 antigens with the effector cells 2• The commonly expressed view 3 is that the effector T cells recognise an antigen created by an interaction of H-2K or H-2D antigen molecules with viral protein. To obtain further support for this notion, Koszinowski and Erd show convincingly that anti-H-2 serum blocks killing when it is directed against the target cells, but not when directed against the effector cells. An unfortunate nomen-clature (for example, anti-H-2kk for (H_2d/k x H_2bb) anti-H-2kk) gives the impression that the sera are directed against the antigens of the whole H-2 complex, when in fact both antisera used are directed only against the K end of the H-2 complex. Thus the H-2D antigens of the effector cells are still free, and one cannot rule out the alternative hypo-thesis!, that in order to kill, effector cells have to match up their SD antigens with those of the targets'. On the other hand, cytotoxicity is blocked completely whenever the anti-serum, be it an anti-H-2K or an anti-vaccinia serum, is directed against the target ceHs, and this is taken as evidence for an interaction product being the target. It is important to know whether a similar blocking could be caused by any antiserum directed against the target cells, or only by anti-H-2 or anti-virus serum. Two points are of particular interest in this respect. First, blocking of cytotoxicity is complete although the antisera cover only the K end-if the blocking is as specific as in allograft reactions, where blocking the target antigens of only one end of H-2 hardly affects the killing5, this would mean that vaccinia, unIike LCM and ectromelia virus 2, modifies only the H-2K antigens. Second, one should note the blocking of F 1 target cells. For example, H-2 k effectors do not kill H-2 d targets, but they will kill (dx k)F1 as weIl as H-2 k target cells. Killing of H-2 k is blocked by anti-H-2K\ not by anti-H-2d , while killing of F 1 targets are blocked by both Matters arising Matters Arising is meant as a vehic1e for comment and discus-sion about papers that appear in Nature. The originator of a Matters Arising contribution should initially send his manuscript to the author of the original paper and both parties should, wherever possible, agree on what is to be submitted. Neither contribution nor reply (if one is necessary) should be Jonger than 300 words and the briefest of replies, to the effect that a point is taken, shouJd be considered. antisera. If the H-2 k effectors interact only with modified H-2k antigens on the target ceIls, one should, again by analogy to the specificity in allograft reactions6, not have expected anti-H-2d serum to have any effect on the killing of F 1 target cells by H-2 k effector cells. My comments are based on the assumption that complete blocking is obtained only when all possible effector-target cell interactions are inhibited, and I have overinterpreted the data, if the relationship between percentage 5lCr-release and number of lytic interactions is less quantitative. Tbe field of T-cell mediated immunity to virus infected target cells is fruitful and holds promise of information about the evolutionary significance of histocom-patibility antigens3 • It is therefore impor-tant, before we make conc1usions about mechanisms, to know to what extent the phenomenon is analogous to allograft immunity. KIRSTEN FISCHER LINDAHL lmmunobiology Research Center, 1150 University Avenue, Madison, Wisconsin 53706 1 Koszinowski, U., and Ertl, H .. Nature, 255, 552 (1975). 2 Blanden, R., et al., Nature, 254, 269 (1974). 3 Lennox, E., Nature, 256, 7 (1975). 4 Zinkernagel, R. M., and Doherty, P. C., Nature, 251,5.47 (1974). 5 Nabholz, M., et al., Eur. J. Immun., 4,378 (1974). 6 Cerottini, J.~C., and Brunner, K. T., Adv. Immun., 18,67 (1974). KOSZINOWSKI AND ERTL REPLy-We think that our data1 do not allow the interpretation that serum mediated blocking of ceIl-mediated cytolysis (CMC) of virus infected syngeneic cells refiects an inhibition of all possible effector-target cell interactions. We cannot express this opinion since we find inhibitory activities also with antisera directed against vaccinia virus specific surface antigens 2 • Tbe F 1 fibroblast targets were extremely sensitive for vaccinia infection which led Nature Val. 258 December 11 1975 to high spontaneous and small specific lysis. We are unsure whether the H-2d inhibition in these experiments had a significance, since unspecific blocking occurred tosomeextent(see Fig.l of ref.l). Anyway, xenogenic anti-target cell serum absorbed for H-2 had no specific inhibitory effect. There are indeed indications that, in the experimental conditions we used the K end is the essential target. When we tested an anti-H-2Dk serum «H-2b x H-2d) anti-Kd D k ) we found minimal blocking activities. These resuIts can be explained by two possible mechanisms. Vaccinia virus alters mainly K-end antigens so that these modified antigens can form a target far the T cell. On the other hand it is possible that T cells predominantly attack K-end alterations. Comparable results con-cerning different inhibitory activity on T-cell mediated kiIling by anti-K-end or D-end sera have recently been described in a tumour situation3 • In the ectromelia system some mouse strains (BlO.A (2R), BIO.A (4R» react more strongly at the K end'. Shearer et al. 5 ,6 describe effector cell activity against TNP-modified cells absolutely restricted to the K end in two mouse strains while other strains recognise the TNP-modified D end as weIl. Restriction of CMC can therefore be dependent on the target ceUS,6, the modifying agent and the mouse strain used, so that at present no generalised answer about K- or D-end specificity is possible. We think that the intimacy hypothesis7 of matching unaltered self antigens is unlikely. In addition to the arguments of Zinkernagel and Doherty8 we found that the target antigen in the vaccinia infection for the CL has a elose physical relation-ship to SD antigensi. Second, enzymatic reduction of H-2 antigens reduces CMC without affecting anti-vaccinia antibody media ted cytolysis (Erd and Koszinowski, unpublished) and third, expression of the H-2 alloantigens is altered detectably by reduced serum absorbing capacity and inhibited allogenic CMC9,lO. The latter observation especiaIly, argues against the possibility of matching normal self antigens as aprerequisite for the recogni-tion of new antigenic determinants. Hygiene-Institut der Universität, Kreuzbergring, West Germany 1 Koszinowski, U., and Ertl, H., Nall/re, 255, 552 (1975). 2 Koszinowski, U., and Thomssen, R., Eur. J. Immun., 5, 245 (1975). 3 Germain, R. N., Dorf, M. E., and Benacerraf, B., J. exp. Med., 142, 1023 (1975). 4 Blanden, R. V., et al., Nature, 254,269 (1975). 5 Shearer, G. M., Rehn, T. G., and Garbarino, C. A' J J. exp. Med., 141, 1348 (1975). 6 Schmitt·Verhulst, A.-M., and Shearer, G. M., J. exp. Med., 142, 914 (1975). 7 ZinkernageJ, R. M., and Doherty, P. V., Nature, 248,701 (1974). 8 Zinkernagel, R. M., and Doherty, P. C., Nature, 251, 547 (1974). 9 Gardner, r. n. t Bowern, N. A., and Blanden, R. V., Eur. J. Immun., 5, 122 (1975). 10 Koszinowski, U., and Ertl. H., Nature, 257, 596 (1975). 

H-2 antigen restriction of viral infection (reply)

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H-2 antigen restriction of viral infection (reply)

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