Biomedical subjects

H Kiyomi Komori

Publications and source records attributed to H Kiyomi Komori.

3 recordsLinked to original sources

PubMed2006

Epithelial and mucosal gamma delta T cells.

Although they constitute a small part of the circulating lymphocyte population, gammadelta T cells are found in high abundance on mucosal and epithelial surfaces. These gammadelta T cells are activated in response to stress to the surrounding tissue and perform a number of functions depending upon the location and type of stress that has occurred. Roles elucidated recently for gammadelta T cells include modulation of epithelial homeostasis through insulin-like growth factor-1 and keratinocyte growth factor, lysis of cytomegalovirus-infected cells, and recruitment of inflammatory cells to sites of tissue damage. Recent advances have provided an understanding of the development of mucosal and skin gammadelta T cells and their roles in restoring and maintaining tissue integrity.

Animals↗

PubMed2005

Dendritic epidermal T-cell activation.

Although gammadelta T cells compose a small proportion of lymphocytes in lymphoid compartments and peripheral blood, they are the major T-cell population present in epithelial tissues. However, the role played by gammadelta TCR expressing intraepithelial lymphocytes (IEL) has been enigmatic. The location of tissue-resident IEL suggests that they are important members of the first line of defense against insult for organs exposed to the environment, including the skin, gut, lungs, and reproductive system. Dendritic epidermal T cells (DETC) are the skin-resident gammadeltaIEL and serve as a model system for gammadeltaIEL in other locations. DETC have demonstrated importance in the modulation of immune responses, surveillance and repair of tissue, and resistance to infection. This work discusses recent developments in understanding DETC activation.

Animals↗

PubMed2004

The long third complementarity-determining region of the heavy chain is important in the activity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5.

The human monoclonal antibody 2F5 neutralizes primary human immunodeficiency virus type 1 (HIV-1) with rare breadth and potency. A crystal structure of a complex of 2F5 and a peptide corresponding to its core epitope on gp41, ELDKWAS, revealed that the peptide interacts with residues at the base of the unusually long (22-residue) third complementarity-determining region of the heavy chain (CDR H3) but not the apex. Here, we perform alanine-scanning mutagenesis across CDR H3 and make additional substitutions of selected residues to map the paratope of Fab 2F5. Substitution of residues from the base of the H3 loop or from CDRs H1, H2, and L3, which are proximal to the peptide, significantly diminished the affinity of Fab 2F5 for gp41 and a short peptide containing the 2F5 core motif. However, nonconservative substitutions to a phenylalanine residue at the apex of the H3 loop also markedly decreased 2F5 binding to both gp41 and the peptide, suggesting that recognition of the core epitope is crucially dependent on features at the apex of the H3 loop. Furthermore, substitution at the apex of the H3 loop had an even more pronounced effect on the neutralizing activity of 2F5 against three sensitive HIV-1. These observations present a challenge to vaccine strategies based on peptide mimics of the linear epitope.

Amino Acid Sequence↗