inhibitory receptor (KIR) gene sequence repertoires. Tissue Antigens

,

–

Di Lorenzo, G., Balistreri, C.R., Candore, G., Cigna, D., Colombo, A., Colonna Romano, G., Colucci, A.T., Gervasi, F., Listi, F., Potestio, M., Caruso, C.,

Granulocyte and natural killer activity in the elderly. Mech. Ageing Dev.

,

–

Dohring, C., Samaridis, J., Colonna, M.,

Alternatively spliced forms of human inhibitory receptors. Immunogenetics

(

),

–

were all identified as positive for the KIR2DS1 gene. A number of studies have suggested that the 2DS1 locus may in fact be an unconfirmed allele of the 2DS4 gene (Hsu et al., 2002a,b), while others report results that do not support this hypothesis indicating 2DS4 as a ‘distinct locus’ (Wilson et al., 2000; Norman et al., 2001). Until there is resolution of this issue and with respect to the present study, 2DS1 must be treated as an independent gene locus. Moreover, all studies to date have treated 2DS4 as an independent gene locus. This controversy highlights the work that still needs to be performed on the polygenic/polymorphic KIR loci to fully elucidate the genetic organisation and functionality of these NK cell receptors. Notably, when the frequency of the 2DS1 gene was examined in an aged and young control group no association was observed (unpublished data).

The KIR loci is located in the leukocyte receptor cluster on chromosome 19q13, a region previously associated with successful ageing in the Irish at the Apo-E loci (Rea et al., 2001). Although, no association was demonstrated in this study the polygenic and polymorphic nature of the KIR loci, and primary role of NK cells in response to viral/bacterial infections and tumours warrants more detailed attention. Considering the pivotal role KIRs may play in the innate immune response, it would be of great interest to repeat this analysis in centenarians who are believed to retain optimal immune function, with this study examining the frequency only in a cohort of successfully aged octogenarians and nonagenarians.

A study is presently underway to evaluate the role of genetic variation across the KIR gene network in immuno- senescence, and to elucidate the true influence of KIR polymorphism on longevity.

Maxwell, L.D., Williams, F., Meenagh, A., Middleton, D.,

Investigation of killer cell immunoglobulin-like receptor gene diversity II. KIR

DS

Hum. Immunol. (in press). Middleton, D., Curran, M., Maxwell, L.,

Natural killer cells and their receptors. Transpl. Immunol.

,

–

Miyaji, C., Watanabe, H., Toma, H., Akisaka, M., Tomiyama, K., Sato, Y., Abo, T.,

Functional alteration of granulocytes, NK cells, and Natural Killer T cells in centenarians. Hum. Immunol.

,

–

Norman, P.J., Stephens, H.A., Verity, D.H., Chandanayingyong, D., Vaughan, R.W.,

Distribution of natural killer cell immunoglo- bulin-like receptor sequences in three ethnic groups. Immunogenetics

,

–

Ogata, K., An, E., Shioi, Y., Nakamura, K., Luo, S., Yokose, N., Minami, S., Dan, K.,

Association between natural killer cell activity and infection in immunologically normal elderly people. Clin. Exp. Immunol.

,

–

Rea, I.M., M

aster, D., Woodside, J.V., Young, I.S., Archbold, G.P., Linton, T., Lennox, S., M

ulty, H., Harmon, D.L., Whitehead, A.S.,

Community-living nonagenarians in Northern Ireland have lower plasma homocysteine but similar methylenetetrahydrofolate reductase thermolabile genotype prevalence compared to

–

-year-old sub- jects. Atherosclerosis

,

–

Rea, I.M., Mc Dowell, I., M

aster, D., Smye, M., Stout, R., Evans, A.,

MONICA group (Belfast). Monitoring of Cardiovascular trends

Acknowledgements

We are grateful to the following organisations for their support of this work: The R&D Office of the Health and Personal Social Services (Northern Ireland) and the Depart- ment of Employment and Learning (Northern Ireland). L.D. Maxwell is a recipient of the Dunville Scholarship awarded by Queens University Belfast. We are grateful to all the participants of the study for there time and Patience.

References

Biassoni, R., Cantoni, C., Falco, M., Pende, D., Millo, R., Moretta, L., Bottino, C., Moretta, A.,

Human natural killer cell activating receptors. Mol. Immunol.

,

–

Bruunsgaard, H., Pedersen, A.N., Schroll, M., Skinhoj, P., Pedersen, B.K.,

Decreased natural killer activity is associated with atherosclerosis in elderly humans. Exp. Geront.

,

–

Crum, K.A., Logue, S.E., Curran, M.D., Middleton, D.,

Development of a PCR-SSOP approach capable of defining the natural killer cell

Biassoni, R., Cantoni, C., Falco, M., Pende, D., Millo, R., Moretta, L., Bottino, C., Moretta, A., 2000. Human natural killer cell activating

Ross et al. / Experimental Gerontology 39 (2004) 801–805

the Belfast Elderly Longitudinal Free-living Ageing Study (BEL- FAST). Mech. Ageing Dev.

(

),

–

Sansoni, P., Cossarizza, A., Brianti, V., Fagnoni, F., Snelli, G., Monti, D., Marcato, A., Passeri, G., Ortolani, C., Forti, E., Fagiolo, U., Passeri, M., Franceschi, C.,

Lymphocytesubsets and natural killer cell activity in healthy old people and centenarians. Blood

(

),

–

Shilling, H.G., Lienert-Weidenbach, K., Valiante, N.M., Uhrberg, M., Parham, P.,

Evidence for recombination as a mechanism for KIR diversification. Immunogenetics

,

–

Shilling, H.G., Young, N., Guethlein, L.A., Cheng, N.W., Gardiner, C.M., Tyan, D., Parham, P.,

Genetic control of human NK cell repertoire. J. Immunol.

(

),

–

Solana, R., Pawelec, G.,

Molecular and cellular basis of

Solana, R., Alonso, M.C., Pena, J., 1999. Natural Killer cells in healthy aging. Exp. Gerontol. 34, 435–443.

aging. Exp. Gerontol.

,

–

Uhrberg, M., Valiante, N.M., Shum, B.P., Shilling, H.G., Weidenbach, K., Corliss, B., Tyan, D., Lanier, L.L., Parham,

Human diversity in killer cell inhibitory receptor Immunity

,

–

Wilson, M.J., Torkar, M., Haude, A., Milne, S., Jones, T., Sheer, D., S., Trowsdale, J.,