SUMMARY REPORTS OF EXCHANGE SCIENTISTS

(1) Hiroshi Hamada
Faculty of Medicine, University of Tokyo

SPONSOR AND HOST INSTITUTION:
Dr. Rudolf Jaenisch
Whitehead Institute
DATES OF VISIT: March 25-April 4, 1991

SUMMARY OF ACTIVITIES:
A) In Whitehead Institute (Dr. Jaenisch's Lab.)
1. I was able to watch the procedures for the ES cell-mediated gene targeting; how to maintain ES cells in good condition, how to design a targeting vector, how to introduce the vector into ES cells, how to select and manipulate the desired targeted cells, how to microinject the targeted cells into blastocyst, how to select and maintain transgenic mice. Those techniques were shown by Dr. M. Rudnicki, a post-doc in Dr. Jaenisch's lab.
2. We are collaborating with Dr. Jaenisch's lab, on the project aiming to knock out the oct3 gene, a gene that we have recently identified and thought to be important for early embryogenesis. This project was initiated about six months ago, but unfortunately the targeted ES cells have not been obtained yet. The problem seems to be the design of the targeting vector, so a new vector has been constructed and has been used for ES cells.
3. I had an opportunity to participate in the Research Meeting of the Dr. Jaenisch's lab. It appeared that the ES cell-mediated gene targeting is a routine work in his lab.
4. I gave an informal seminar in his lab. The title was "Oct 3, a master regulator of early embryogenesis." Many people seemed to be interested in the talk, and gave me invaluable comments.

B) In NIH/FCRC (Dr. N. Jenkins's lab.)
1. I met with Dr. Neal Copeland, and learned chromosome mapping technique by using interspecies backcross. Since it is rapid and efficient, it seemed to be a very powerful technique for chromosome mapping.
2. We had sent two probes to Dr. Jenkins's lab, for mapping. The results have been obtained, and their chromosomal location has been determined.



(2) Hideo Yamagishi
Department of Biophysics, Faculty of Science
Kyoto University

SPONSOR AND HOST INSTITUTION:
Dana-Farber Cancer Institute
Harvard Medical School
DATES OF VISIT: September 29-October 21, 1990

SUMMARY OF ACTIVITIES:
I have visited several Institutes in Boston and Cambridge to exchange the information on "Gene rearrangements and tumor antigen recognition by T-cell." At the Dana-Farber Cancer Institute, Harvard Medical School (Host: Michael B: Brenner), I gave a special seminar "Immunoglobulin gene rearrangements and circle formation" on October 3 and an informal laboratory seminar “TCR gamma gene rearrangements and circle formation" on October 4. I talked with Dr. K-N. Tan on the restricted usage of TCR V alpha3 in arsonate-specific HTL. In collaboration with Dr. O. Kanagawa, University of Washington, St. Louis, she suggested the availability of anti V alpha3 mAb for characterization of our CTL clones specific for FBL-3 tumor antigen. We received the mAb and the CTL characterization is now successfully ongoing due to the mAb. I discussed with Dr. J. Sklar on the biological significance of TCR gamma/delta chimeric recombination ensuing translocation, Dr. H. Saito on the antitumor role of protein tyrosine phosphatase and Dr. D. Weaver on the role of recombinase in SCID mouse, respectively.
In Tufts University, I discussed with Dr. E. Selsing on the interchromosomal class switch recombination, Dr. N. Rosenberg on V to DJH arrest by absence of sterile transcription of VH and Dr. H. Brodeur on dispersed VH usage and preferential Vk4 usage, respectively. In MIT (Host: D. Raulet), I gave a special immunology seminar "Immunoglobulin gene rearrangements and circle formation" on October 5. I received anti-C gamma 2 Ab as gifts in Tonegawa's laboratory to characterize our thymic lymphoma cell lines. In Harvard University, Department of Biology, I discussed with Dr. J. Wang the role of topoisomerases on TCR and Ig gene rearrangements.
In University of Chicago, The Ben May Institute (Host: Jeffrey A. Bluestone), I gave a special weekly seminar "Immunoglobulin gene rearrangements and circle formation" and an informal laboratory seminar on the rearrangement pathway in gamma/delta and alpha/beta T-cells on October 8. I received anti-C gamma4 Ab as gifts in Bluestone's laboratory to characterize our thymic lymphoma cell lines. I also learned from Dr. F. Fitch about the heterogeneity of HTL and discussed with Drs. J. Quintans, U. Storb, J. Miller, J. Urban and D.A. Rowley.
I visited Dr. F. Lilly of Albert Einstein College of Medicine, New York, and exchanged the information on virus antigen represented on FBL-3 tumor. We agreed on collaborate on findinf the FBL-3 tumor antigen recognized by our CTL clones. In Columbia University, College of Physicians and Surgeons (Host: Frederick Alt), I gave an informal laboratory seminar "Immunoglobulin gene rearrangements and circular DNA formation" on October 10. I attended on The Irvington Institute 75th Anniversary Symposium "Immunology in the 21st century" held at New York City on October 11-12.
In California Institute of Technology, Division of Biology (Host: Leroy Hood), I gave a special seminar "Antibody and T-cell receptor genes" on October 15. I discussed with Dr. L. Hood on the possibility to collaborate in Human Frontier Science Projects of DNA sequencing. I visited Dr. M. Kronenberg of UCLA and discussed the recombinases responsible for gene rearrangements.
In UCSD, Department of Biology (Host: Stephen M. Hedrick), I gave a seminar "Immunoglobulin gene rearrangements and circular formation" on October 18. After that, I discussed with Dr. S. M. Hedrick on the discrepancy on gamma/delta and alpha/beta T-cell TCR rearrangements between Baltimore's and our groups. In The Salk Institute (Host: Ronald Evans), I gave a seminar "Immunoglobulin gene rearrangements and circle formation" on October 19. Finally, I visited Research Institute of Scripps Clinic to see Drs. M. B. A. Oldstone and Y. Yanagi and discussed the restricted V segment usage in TCR of CTL specific for a major epitope of lymphocytic choriomeningitis virus. I received the MHC H2-D^b presenting cell MC57 as gifts to characterize our FBL-3 tumor antigen.



(3) Yasunobu Yoshikai
Department of Immunology
Medical Institute of Bioregulation

SPONSOR AND HOST INSTITUTION:
Jeffrey, A Bluestone
Associate Professor
University of Chicago
DATES OF VISITS: October 16-22, 1990

SUMMARY OF ACTIVITIES
1. LECTURE
I have talked about our study on the role of T cells bearing gamma/delta T cell receptor (TcR) in immunopathology. My talk was consisted of two parts; the first was about the protective role of gamma/delta TcR-bearing T cells in infection with Mycobacteria bovis (Bacilus Calmette Guerin) and Listeria monocytogenes in mice and the second was the role of gamma/delta TcR-bearing T cells in the induction of autoimmune disease in mice. There were many questions and suggestions about my talk. To determine whether gamma/delta TcR-bearing T cells really play an important role in protection against the bacterial infection, it was pointed out that we should examine the in vivo effect of anti-gamma/delta TcR monoclonal antibody (mAb) on the protection against the bacterial infection. Furthermore, it was suggested that immunohistochemical examination in pathological lesions may be useful to elucidate the role of gamma/delta TcR-bearin T cells in induction of autoimmune disease

2. DISCUSSION
I discussed with eight researchers in Dr. J.A. Bluestone's lab their recent projects including gamma/delta TcR gene-transgenic mice, positive and negative selection of gamma/delta-TcR-bearing T cells in the thymus and in vivo effect of anti-gamma/delta TcR-bearing T cells on antitumor immunity.

3. EXPERIMENTS
I learned how to purify anti-gamma/delta TcR mAb from the culture supernatants of the hybridoma, how to make a single gamma/delta TcR bearing T cell clone and how to make gamma/delta TcR gene transgenic mice. Furthermore, I observed the experiment with anti-gamma/delta TcR mAb in vivo.

4. COLLABORATION
Finally I talked with Dr. J.A Bluestone about our collaborative works using anti-gamma/delta TcR mAb in vivo. We are planning to examine the effect of in vivo treatment with anti-gamma/delta TcR mAb on protection against infection with BCG or Listeria monocytogenes and on anti-tumor immunity and to exchange the experimental data. I was provided hybridomas producing anti-gamma/delta TcR mAb b Dr. B.A Bluestone.
I thank Japan Society for the Promotion of Science for supporting the visit to University of Chicago.