Something Happens; A Brief History of TCR Signal Transduction

If truth be told, when asked to write this chapter my first reaction was not positive; I thought “I am too young! (aren’t I?).” However, when I considered the Editor’s request, I realized that I had been fortunate to have had my formative scientific years coincide with extraordinary advances in our understanding of the T-cell receptor (TCR) signaling and to have been part of a laboratory that contributed to this field in a major way. First though, a disclaimer: this is a personal and biased view of this field; I was not an experienced scientist witnessing these discoveries, I was just a “post-doc.” So the perspective may be idiosyncratic, and I apologize at the outset for my “Bethesda-centricity.” Nonetheless, to begin Part IV, I would like to review what I viewed as the major breakthroughs that led to our present comprehension of TCR signal transduction, including how the understanding of the structure of the TCR came about and how that, in turn, led to insights into signaling.