I m m u n o l o g y Today, voL 8, No. 1 I, 1987
MHC class I antigens and somatic mutants Sir, I read with interest the hypothesis offered by T.V. Rajan to explain a possible role for class I major histocompatibility complex (MHC) antigens in the elimination of somatic mutants (Immunol. Today, 1987, 8, 171). I believe, however, that his conclusions fail to explain the apparently endless number of tumor-specific transplantation antigens (TSTA) or turn- variants of mouse neoplasms ~. I consider that, even in tumor cells, dass I antigens exist to control abnormal peptides expressed within cells, forming with them an iinmunogenic complex which in turn stimulates T lymphocytes to eliminate the cells producing the 'wrong' material. This is supported by the observation that cytosolic proteins may be even more immunogenic l and contain more TSTA determiL~nants than do cell surface mem-
.rt.de,/s #d
branes 2, a finding which suggests that TSTA 'precursors' originate in the cytoplasm of cancer cells. It is unlikely, however, that more than 100 different molecules (a minimum estimate of the number of different TSTAs calculated to exist in a tumor population in the same strain of mice t) can be altered without killing the cell. I propose that only a limited number of gene families endowed with the ability to generate diversity need be affected by the carcinogen to give rise to hundreds of slightly abnormal peptides. In support of this is the fact that the TSTA molecules so far characterized belong to class I-like gene products 3. endogenous retroviral proteins4, s, immunoglobulinlike prcducts 6, heat-shock proteins 7 and a few others 8. These protein families have in common an ability either to be inserted on the cell surface or to deposit on it, and can thus interact with MHC products. Point-mutated or rearranged products of these gene families can thus be transferred as peptides to the cell
surface and 'trapped' and transformed into TSTAs or turn-variants by class I MHC molecules.
Giorgio Parmiani Divisionof ExperimentalOncologyD, Istituto NazionaleTumori,Milan20133, Italy
Reference 1 Basombrio, M.A. (1970) CancerRes. 30. 2485-2462 2 Rogers. M.J. and Law, L.W. (1981)1nt. J. Cancer 27, 789-796 3 Phillips, C., McMillan, M, Flood, P.M. et al. (1985)Proc. Natl Acad. Sci. USA 82, 5140-5145 4 Lennox, E.S. Lowe, A.O., Cohn, J. and Evan, C. (1981 ) Transplant. Proc. 13, 1759-1762 $ De Leo, A.B., Chang, K.S.S.,Wivel, N.A. et al. (1982) Int. J. Cancer 29, 687-693 6 Pravtcheva, D.D., De Leo, A.B., Ruddle, F.H. and Old, L.J. (1981)J. Exp. Med. 154, 964-977 7 UIIrich, S.J., Robinson, E.A., Law, LW., Willingham, M. and Appella, E. (1986) Proc NatlAcad. Sci. USA 83, 3121-3125 8 Srivastava, P.K., De Leo, A.B. and Old, L.J. (1986) Proc Natl Acad. Sci. USA 83, 3407-3411
dise t on/ munolo#
The articles in Immunology Today are in widespread demand as teaching material for courses at all levels. To help students have their own copies, Immunology Today is being made available at 30% discount to students enrolled at recognised institutions. A student subscription comprises the monthly issues starting from any month in 1987. Prices include air delivery worldwide. US $35.00, USA and Canada; £21.00, UK; Dfl. 103.00, Europe; Dfl. 121.00, Rest of World. Please start my subscription to Immunology Today from the next available issue in 1987. I enclose my personal cheque for £ ................. /Dfl .................. /$ ................ made out to Elsevier. Name .........................................................................
Signature
.........................................................................
Address ................................................................................................................................................................. ........................................................................................................................................ Postal Code ............... Name of Institution ................................................................................................................................................. Title of course for which you are enrolled .................................................
Date of termination of course ..............
A photocopy of this form must be sent to the appropriate address accompanied by your personal cheque and vahd proof of current student status (photocopy of Student card, letter from Head of Department. etc.) Subscribers to the USA and Canada only (cheque for US $35.00) to
Else~erScJencePublishing Company Inc. Attn: IT Subscriptions. 52 Vanderbilt Avenue, New York. NY 10017. USA
Subscnbers in the UK only (cheque for £2? 00) to
Elsevier Publications (Cambndge) Attn. IT Subscriptions 68 Hills Road, Cambndge CB2 1LA. United Kingdom
Circle no 190 on advertising enquiry form
Subscnbers to the Rest of the World (cheque for 103.00 Dutch gudders (Euro.~e) or 121 O0 Dutch gudders (outside Europe) to
Elsevier Biomedical Press, P G Bo~,548. 1000 AM Amsterdam. The Netherlands
MHC class I antigens and somatic mutants Sir, I read with interest the hypothesis offered by T.V. Rajan to explain a possible role for class I major histocompatibility complex (MHC) antigens in the elimination of somatic mutants (Immunol. Today, 1987, 8, 171). I believe, however, that his conclusions fail to explain the apparently endless number of tumor-specific transplantation antigens (TSTA) or turn- variants of mouse neoplasms ~. I consider that, even in tumor cells, dass I antigens exist to control abnormal peptides expressed within cells, forming with them an iinmunogenic complex which in turn stimulates T lymphocytes to eliminate the cells producing the 'wrong' material. This is supported by the observation that cytosolic proteins may be even more immunogenic l and contain more TSTA determiL~nants than do cell surface mem-
.rt.de,/s #d
branes 2, a finding which suggests that TSTA 'precursors' originate in the cytoplasm of cancer cells. It is unlikely, however, that more than 100 different molecules (a minimum estimate of the number of different TSTAs calculated to exist in a tumor population in the same strain of mice t) can be altered without killing the cell. I propose that only a limited number of gene families endowed with the ability to generate diversity need be affected by the carcinogen to give rise to hundreds of slightly abnormal peptides. In support of this is the fact that the TSTA molecules so far characterized belong to class I-like gene products 3. endogenous retroviral proteins4, s, immunoglobulinlike prcducts 6, heat-shock proteins 7 and a few others 8. These protein families have in common an ability either to be inserted on the cell surface or to deposit on it, and can thus interact with MHC products. Point-mutated or rearranged products of these gene families can thus be transferred as peptides to the cell
surface and 'trapped' and transformed into TSTAs or turn-variants by class I MHC molecules.
Giorgio Parmiani Divisionof ExperimentalOncologyD, Istituto NazionaleTumori,Milan20133, Italy
Reference 1 Basombrio, M.A. (1970) CancerRes. 30. 2485-2462 2 Rogers. M.J. and Law, L.W. (1981)1nt. J. Cancer 27, 789-796 3 Phillips, C., McMillan, M, Flood, P.M. et al. (1985)Proc. Natl Acad. Sci. USA 82, 5140-5145 4 Lennox, E.S. Lowe, A.O., Cohn, J. and Evan, C. (1981 ) Transplant. Proc. 13, 1759-1762 $ De Leo, A.B., Chang, K.S.S.,Wivel, N.A. et al. (1982) Int. J. Cancer 29, 687-693 6 Pravtcheva, D.D., De Leo, A.B., Ruddle, F.H. and Old, L.J. (1981)J. Exp. Med. 154, 964-977 7 UIIrich, S.J., Robinson, E.A., Law, LW., Willingham, M. and Appella, E. (1986) Proc NatlAcad. Sci. USA 83, 3121-3125 8 Srivastava, P.K., De Leo, A.B. and Old, L.J. (1986) Proc Natl Acad. Sci. USA 83, 3407-3411
dise t on/ munolo#
The articles in Immunology Today are in widespread demand as teaching material for courses at all levels. To help students have their own copies, Immunology Today is being made available at 30% discount to students enrolled at recognised institutions. A student subscription comprises the monthly issues starting from any month in 1987. Prices include air delivery worldwide. US $35.00, USA and Canada; £21.00, UK; Dfl. 103.00, Europe; Dfl. 121.00, Rest of World. Please start my subscription to Immunology Today from the next available issue in 1987. I enclose my personal cheque for £ ................. /Dfl .................. /$ ................ made out to Elsevier. Name .........................................................................
Signature
.........................................................................
Address ................................................................................................................................................................. ........................................................................................................................................ Postal Code ............... Name of Institution ................................................................................................................................................. Title of course for which you are enrolled .................................................
Date of termination of course ..............
A photocopy of this form must be sent to the appropriate address accompanied by your personal cheque and vahd proof of current student status (photocopy of Student card, letter from Head of Department. etc.) Subscribers to the USA and Canada only (cheque for US $35.00) to
Else~erScJencePublishing Company Inc. Attn: IT Subscriptions. 52 Vanderbilt Avenue, New York. NY 10017. USA
Subscnbers in the UK only (cheque for £2? 00) to
Elsevier Publications (Cambndge) Attn. IT Subscriptions 68 Hills Road, Cambndge CB2 1LA. United Kingdom
Circle no 190 on advertising enquiry form
Subscnbers to the Rest of the World (cheque for 103.00 Dutch gudders (Euro.~e) or 121 O0 Dutch gudders (outside Europe) to
Elsevier Biomedical Press, P G Bo~,548. 1000 AM Amsterdam. The Netherlands
