Additional Reading Summary, Week 7

Sorry for the late post. There were so many articles that it took a little longer than expected. Here is my summary of the articles.

“The T-lymphocyte antigen receptor—paradigm lost”
Jens Jensenius and Alan Williams

This article speaks about the ongoing paradigm shift from the idea T-cells were essentially the same as membrane bound antibodies. It was thought for quite some time that if the T-cell receptor was so similar to the immunoglobulin, identifying structures with V-domains on T-lymphocytes would allow scientists to identify the receptor. The article talks about why this paradigm should be shifted due to the disparity between immunoglobulin and the T-cell receptor. For example, the T-cell receptor is unable to directly bind unprocessed antigen. In addition, the receptor’s co-recognition of the histocompatibility complex along with foreign antigen indicates the necessity for the paradigm shift away from a foundation on immunoglobulin.


“On the Trail of the T-cell Receptor”
Mark Davis

Dr. Davis provides a great summary of the work that he and his lab did to be the first to clone the T-cell receptor. He gives a brief history of T-cells and the many theories that were proposed in regards to the receptor, such as the two receptor model, in which one receptor recognized antigen and the other the MHC. Dr. Davis recounts his decision to work on the T-cell receptor, a looming unknown in immunology, by applying what he knew best from CalTech, Cot curves and subtractive hybridization. Luckily, he determined that there was only a 2% difference between the B-cells and T-cells (approximately 100-200 genes). Therefore, using a library of cDNA probes to screen the B and T-cell libraries, the gene was finally narrowed down using the last clone, TM-86. Dr. Davis then moved to Stanford from the NIH to continue the research, and the process kicked into full gear. Once he presented the results at an immunology conference in Tokyo, the subject exploded, with countless other researchers desperately working to find the other chains of the receptor. Ultimately, Dr. Davis gives gave a great personal review of the process that went into discovering the T-cell receptor and the “breaching a major bottleneck in the understanding of the mechanism of the T-cell.”


“Isolation of cDNA clones encoding T cell-specific membrane-associated proteins”
Mark Davis, et al.
“Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins”
Mark Davis, et al.


These two articles summarize the findings of Dr. Davis and his lab in more detail. The first article entitled, “Isolation of cDNA…” was the first paper to hint that the T-cell receptor gene had been found. Dr. Davis and his lab had determined that one of the cloned DNA copies of mRNA expressed only in T-cells, which was also a membrane bound protein, also hybridized in a region of the genome known to rearrange in T-cell lymphomas and hybridomas. These factors all indicated that this gene did in fact code for the surface T-cell receptor.

The second article recounts the comparison of this T-cell specific cDNA with cross-reacting cDNA clones from a thymocyte library. Their subsequent reactivity indicated that a variable, constant, and joining region were present within the gene segment and were very similar to those segments found in immunoglobulin proteins. Somatic rearrangement had already been observed, and further supported that this isolated gene segment encoded one of the chains of the T-cell receptor.