The four distinct T-cell antigen receptor polypeptides (alpha, beta, gamma, delta) form two different heterodimers (alpha:beta and gamma:delta) that are very similar to immunoglobulins in primary sequence, gene organization and modes of rearrangement. Whereas antibodies have both soluble and membrane forms that can bind to antigens alone, T-cell receptors exist only on cell surfaces and recognize antigen fragments only when they are embedded in major histocompatibility complex (MHC) molecules. Patterns of diversity in T-cell receptor genes together with structural features of immunoglobulin and MHC molecules suggest a model for how this recognition might occur. This view of T-cell recognition has implications for how the receptors might be selected in the thymus and how they (and immunoglobulins) may have arisen during evolution.

T-cell antigen receptor genes and T-cell recognition.

Signal sequences: The limits of variation

The ability to adapt to altered availability of free water is a fundamental property of living cells. The principles underlying osmoadaptation are well conserved. The yeast Saccharomyces cerevisiae is an excellent model system with which to study the molecular biology and physiology of osmoadaptation. Upon a shift to high osmolarity, yeast cells rapidly stimulate a mitogen-activated protein (MAP) kinase cascade, the high-osmolarity glycerol (HOG) pathway, which orchestrates part of the transcriptional response. The dynamic operation of the HOG pathway has been well studied, and similar osmosensing pathways exist in other eukaryotes. Protein kinase A, which seems to mediate a response to diverse stress conditions, is also involved in the transcriptional response program. Expression changes after a shift to high osmolarity aim at adjusting metabolism and the production of cellular protectants. Accumulation of the osmolyte glycerol, which is also controlled by altering transmembrane glycerol transport, is of central importance. Upon a shift from high to low osmolarity, yeast cells stimulate a different MAP kinase cascade, the cell integrity pathway. The transcriptional program upon hypo-osmotic shock seems to aim at adjusting cell surface properties. Rapid export of glycerol is an important event in adaptation to low osmolarity. Osmoadaptation, adjustment of cell surface properties, and the control of cell morphogenesis, growth, and proliferation are highly coordinated processes. The Skn7p response regulator may be involved in coordinating these events. An integrated understanding of osmoadaptation requires not only knowledge of the function of many uncharacterized genes but also further insight into the time line of events, their interdependence, their dynamics, and their spatial organization as well as the importance of subtle effects.

Osmotic Stress Signaling and Osmoadaptation in Yeasts

The search for genetic damage in neoplastic cells now occupies a central place in cancer research. Diverse examples of such damage are in hand, and they in turn hint at biochemical explanations for neoplastic growth. The way may be open to solve the riddles of how normal cells govern their replication and why cancer cells do not.

https://science.sciencemag.org/content/sci/235/4786/305.full.pdf

The molecular genetics of cancer

The immune system is an organization of cells and molecules with specialized roles in defending against infection. There are two fundamentally different types of responses to invading microbes. Innate (natural) responses occur to the same extent however many times the infectious agent is encountered, whereas acquired (adaptive) responses improve on repeated exposure to a given infection. The innate responses use phagocytic cells (neutrophils, monocytes, and macrophages), cells that release inflammatory mediators (basophils, mast cells, and eosinophils), and natural killer cells. The molecular components of innate responses include complement, acute-phase proteins, and cytokines such as the interferons.

The immune system. First of two parts.

Two related, but distinct, cDNA clones have been isolated and sequenced from a functional murine cytotoxic T-lymphocyte clone. The genes corresponding to these cDNA are expressed and rearranged specifically in T cells and both have similarities to immunoglobulin variable and constant region genes. It is concluded that these genes code for the two subunits of the heterodimeric antigen receptor on the surface of the T cell; its complete deduced primary structure is presented.

Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences.

En plus des deux genes prealablement identifies et exprimes dans un clone de lymphocytes T cytotoxiques, on identifie un troisieme gene egalement rearrange et exprime dans le meme clone. Ce nouveau gene presente une diversite clonale, code pour une chaine polypeptidique qui contient des domaines variable et constant de type immunoglobuline, porte des sites de N-glycosylation potentiels et constitue un candidat particulierement vraisemblable pour le gene codant pour la sousunite alpha du recepteur heterodimere pour l'antigene de ce clone cellule T

A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes.

In contrast to B cells or their antibody products, T lymphocytes have a dual specificity, for both the eliciting foreign antigen and for polymorphic determinants on cell surface glycoproteins encoded in the major histocompatibility complex (MHC restriction)1–4. The recent identification of T-cell receptor glycoproteins5–7 as well as the genes encoding T-cell receptor subunits will help to elucidate whether MHC proteins and foreign antigens are recognized by two T-cell receptors or by a single receptor. An important feature of MHC restriction is that it appears to be largely acquired by a differentiating T-cell population under the influence of MHC antigens expressed in the thymus8–10, suggesting that precursor T cells are selected on the basis of their reactivity with MHC determinants expressed in the host thymus9–11. To understand this process of ‘thymus education’, knowledge of the developmental regulation of T-cell receptor gene expression is necessary. Here we report that whereas messenger RNAs encoding the β-and γ-subunits are relatively abundant in immature thymocytes, α mRNA levels are very low. Interestingly, whereas α mRNA levels increase during further development and β mRNA levels stay roughly constant, γ mRNA falls to very low levels in mature T cells, suggesting a role for the γ gene in T-cell differentiation.

Developmental regulation of T-cell receptor gene expression.

https://www.cell.com/cell/pdf/0092-8674(85)90140-0.pdf

Structure, organization, and somatic rearrangement of T cell gamma genes

A tissue-specific transcriptional enhancer element that is associated with the human immunoglobulin heavy-chain locus is defined. In a non-Hodgkin's lymphoma that contains a translocated c-myc gene this enhancer is retained on the 14q+ chromosome and occurs within sequences shown to activate previously cryptic promoters of the c-myc gene.

/pdf/activation-of-a-translocated-human-c-myc-gene-by-an-enhancer-57a8o3uonn.pdf

Haruo Saito

Papers

Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences.

A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes.

Developmental regulation of T-cell receptor gene expression.

Structure, organization, and somatic rearrangement of T cell gamma genes

Activation of a translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus