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. 1970 Oct 1;132(4):613–622. doi: 10.1084/jem.132.4.613

CELLULAR BASIS OF THE GENETIC CONTROL OF IMMUNE RESPONSES TO SYNTHETIC POLYPEPTIDES

I. DIFFERENCES IN FREQUENCY OF SPLENIC PRECURSOR CELLS SPECIFIC FOR A SYNTHETIC POLYPEPTIDE DERIVED FROM MULTICHAIN POLYPROLINE ([T, G]-PRO--L) IN HIGH AND LOW RESPONDER INBRED MOUSE STRAINS

Edna Mozes 1, G M Shearer 1, Michael Sela 1
PMCID: PMC2138860  PMID: 5534158

Abstract

SJL mice are high responders to the synthetic multichain polypeptide antigen (T,G)-Pro--L, whereas DBA/1 mice are low responders (10, 11). In order to determine whether the genetic control of immune response can be correlated with the number of antigen-sensitive precursor cells, spleen cell suspensions from normal and immunized SJL and DBA/1 donor mice were transplanted into lethally X-irradiated syngeneic recipients (incapable of immune response) along with (T, G)-Pro--L. Anti-(T, G)-Pro--L responses (donor-derived) were assayed in the sera of the hosts 12–16 days later. By transplanting graded and limiting numbers of spleen cells, inocula were found which contained one or a few antigen-sensitive precursors reactive with the immunogen. Using this method to estimate the relative numbers of such cells for the high responder SJL strain, one precursor was detected in ∼1.3 x 106 and ∼7.2 x 106 spleen cells from immunized and normal donors, respectively. In contrast, one precursor was detected in about 30 x 106 spleen cells from low responder DBA/1 mice, irrespective of whether the donors had been immunized. These results indicate that the genetic control of immunity to the synthetic polypeptide antigen investigated is directly correlated to the relative number of precursor cells reactive with the immunogen in high and low responder strains.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brown R. A., Makinodan T., Albright J. F. Significance of a single-hit event in the initiation of antibody response. Nature. 1966 Jun 25;210(5043):1383–1384. doi: 10.1038/2101383a0. [DOI] [PubMed] [Google Scholar]
  2. Claman H. N., Chaperon E. A., Triplett R. F. Immunocompetence of transferred thymus-marrow cell combinations. J Immunol. 1966 Dec;97(6):828–832. [PubMed] [Google Scholar]
  3. Cudkowicz G., Shearer G. M., Priore R. L. Cellular differentiation of the immune system of mice. V. Class differentiation in marrow precursors of plaque-forming cells. J Exp Med. 1969 Sep 1;130(3):481–491. doi: 10.1084/jem.130.3.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gasser D. L. Genetic control of the immune response in mice. I. Segregation data and localization to the fifth linkage group of a gene affecting antibody production. J Immunol. 1969 Jul;103(1):66–70. [PubMed] [Google Scholar]
  5. Green I., Paul W. E., Benacerraf B. The behavior of hapten-poly-L-lysine conjugates as complete antigens in genetic responder and as haptens in nonresponder guinea pigs. J Exp Med. 1966 May 1;123(5):859–879. doi: 10.1084/jem.123.5.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jaton J. C., Sela M. Role of optical configuration in the immunogenicity and specificity of synthetic antigens derived from multichain polyproline. J Biol Chem. 1968 Nov 10;243(21):5616–5626. [PubMed] [Google Scholar]
  7. KANTOR F. S., OJEDA A., BENCARERRAF B. Studies on artifical antigens. I. Antigenicity of DNP-polylysine and DNP copolymer of lysine and glutamic acid in guinea pigs. J Exp Med. 1963 Jan 1;117:55–69. doi: 10.1084/jem.117.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kennedy J. C., Till J. E., Siminovitch L., McCulloch E. A. The proliferative capacity of antigen-sensitive precursors of hemolytic plaque-forming cells. J Immunol. 1966 Jun;96(6):973–980. [PubMed] [Google Scholar]
  9. LEVINE B. B., BENACERRAF B. GENETIC CONTROL IN GUINEA PIGS OF IMMUNE RESPONSE TO CONJUGATES OF HAPTENS AND POLY-L-LYSINE. Science. 1965 Jan 29;147(3657):517–518. doi: 10.1126/science.147.3657.517. [DOI] [PubMed] [Google Scholar]
  10. LEVINE B. B., OJEDA A., BENACERRAF B. STUDIES ON ARTIFICIAL ANTIGENS. III. THE GENETIC CONTROL OF THE IMMUNE RESPONSE TO HAPTEN-POLY-L-LYSINE CONJUGATES IN GUINEA PIGS. J Exp Med. 1963 Dec 1;118:953–957. doi: 10.1084/jem.118.6.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McDevitt H. O., Benacerraf B. Genetic control of specific immune responses. Adv Immunol. 1969;11:31–74. doi: 10.1016/s0065-2776(08)60477-0. [DOI] [PubMed] [Google Scholar]
  12. McDevitt H. O., Chinitz A. Genetic control of the antibody response: relationship between immune response and histocompatibility (H-2) type. Science. 1969 Mar 14;163(3872):1207–1208. doi: 10.1126/science.163.3872.1207. [DOI] [PubMed] [Google Scholar]
  13. McDevitt H. O. Genetic control of the antibody response. 3. Qualitative and quantitative characterization of the antibody response to (T,G)-A--L in CBA and C57 mice. J Immunol. 1968 Mar;100(3):485–492. [PubMed] [Google Scholar]
  14. McDevitt H. O., Sela M. Genetic control of the antibody response. I. Demonstration of determinant-specific differences in response to synthetic polypeptide antigens in two strains of inbred mice. J Exp Med. 1965 Sep 1;122(3):517–531. doi: 10.1084/jem.122.3.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McDevitt H. O., Sela M. Genetic control of the antibody response. II. Further analysis of the specificity of determinant-specific control, and genetic analysis of the response to (H,G)-A--L in CBA and C57 mice. J Exp Med. 1967 Nov 1;126(5):969–978. doi: 10.1084/jem.126.5.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McDevitt H. O., Tyan M. L. Genetic control of the antibody response in inbred mice. Transfer of response by spleen cells and linkage to the major histocompatibility (H-2) locus. J Exp Med. 1968 Jul 1;128(1):1–11. [PMC free article] [PubMed] [Google Scholar]
  17. Mitchell G. F., Miller J. F. Cell to cell interaction in the immune response. II. The source of hemolysin-forming cells in irradiated mice given bone marrow and thymus or thoracic duct lymphocytes. J Exp Med. 1968 Oct 1;128(4):821–837. doi: 10.1084/jem.128.4.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mosier D. E., Coppleson L. W. A THREE-CELL INTERACTION REQUIRED FOR THE INDUCTION OF THE PRIMARY IMMUNE RESPONSE in vitro. Proc Natl Acad Sci U S A. 1968 Oct;61(2):542–547. doi: 10.1073/pnas.61.2.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mosier D. E., Fitch F. W., Rowley D. A., Davies A. J. Cellular deficit in thymectomized mice. Nature. 1970 Jan 17;225(5229):276–277. doi: 10.1038/225276a0. [DOI] [PubMed] [Google Scholar]
  20. Mozes E., McDevitt H. O., Jaton J. C., Sela M. The genetic control of antibody specificity. J Exp Med. 1969 Dec 1;130(6):1263–1278. doi: 10.1084/jem.130.6.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mozes E., McDevitt H. O., Jaton J. C., Sela M. The nature of the antigenic determinant in a genetic control of the antibody response. J Exp Med. 1969 Sep 1;130(3):493–504. doi: 10.1084/jem.130.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nossal G. J., Cunningham A., Mitchell G. F., Miller J. F. Cell to cell interaction in the immune response. 3. Chromosomal marker analysis of single antibody-forming cells in reconstituted, irradiated, or thymectomized mice. J Exp Med. 1968 Oct 1;128(4):839–853. doi: 10.1084/jem.128.4.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. PORTER E. H., BERRY R. J. THE EFFICIENT DESIGN OF TRANSPLANTABLE TUMOUR ASSAYS. Br J Cancer. 1963 Dec;17:583–595. doi: 10.1038/bjc.1963.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Raidt D. J., Mishell R. I., Dutton R. W. Cellular events in the immune response : analysis and in vitro response of mouse spleen cell populations separated by differential flotation in albumin gradients. J Exp Med. 1968 Oct 1;128(4):681–698. doi: 10.1084/jem.128.4.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shearer G. M., Cudkowicz G. Cellular differentiation of the immune system of mice. 3. Separate antigen-sensitive units for different types of anti-sheep immunocytes formed by marrow-thymus cell mixtures. J Exp Med. 1969 May 1;129(5):935–951. doi: 10.1084/jem.129.5.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shearer G. M., Cudkowicz G., Connell M. S., Priore R. L. Cellular differentiation of the immune system of mice. I. Separate splenic antigen-sensitive units for different types of anti-sheep antibody-forming cells. J Exp Med. 1968 Sep 1;128(3):437–457. doi: 10.1084/jem.128.3.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shearer G. M., Cudkowicz G., Priore R. L. Cellular differentiation of the immune system of mice. II. Frequency of unipotent splenic antigen-sensitive units after immunization with sheep erythrocytes. J Exp Med. 1969 Jan 1;129(1):185–199. doi: 10.1084/jem.129.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]

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