Recognition of influenza virus hemagglutinin by subtype-specific and cross-reactive proliferative T cells: contribution of HA1 and HA2 polypeptide chains

The recognition of influenza virus hemagglutinin (HA) by T lymphocytes was examined by assaying the T cell proliferative response of influenza virus-primed T cells to purified HA of different influenza A subtypes or to isolated heavy (HA1) or light (HA2) polypeptide chains of the HA molecule. The proliferative response to HA was dependent on the activation of an Ly-1+2- subset of T cells and required the presence of nylon wool-adherent, radiation-resistant accessory cells. T cells from mice primed by infection with one strain of type A influenza virus cross-reacted with other purified HA not only of the same subtype as the priming virus but also of serologically distinct subtypes of influenza A (but not B) virus. The response of virus-primed T cells to the homologous HA or to HA of the same subtype was shown to involve recognition of determinants on both the HA1 and the HA2 chains. The recognition of HA of different subtype by cross-reactive T cells appeared to be directed predominantly to determinants on HA2. Because the antibody response to influenza virus HA is not cross-reactive between subtypes and is directed predominantly to determinants on HA1, the present results indicate that at least some of the determinants on HA recognized by T cells are different from those recognized by B cells and that the HA2 chain may be involved primarily in stimulation of T cell rather than B cell immunity.     

Transbilayer distribution of bromine in fluid bilayers containing a specifically brominated analogue of dioleoylphosphatidylcholine

We describe in this paper the transbilayer distribution of the bromines of the specifically halogenated phospholipid 1-oleoyl-2-(9,10-dibromostearoyl)-sn-glycero-3- phosphocholine (OBPC). The distribution was determined by X-ray diffraction of oriented multilayers of mixtures of OBPC and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) at 66% relative humidity by the general approach of Franks et al. (1978) [Nature 276, 530-532]. The bromine distribution of OBPC in the fluid L alpha phase is described accurately by a pair of Gaussian functions located 7.97 +/- 0.27 A from the center of the bilayer with l/e half-widths of 4.96 +/- 0.62 A. We find that OBPC bilayers are accurately described as DOPC bilayers with an additional bromine distribution centered at the position of the double bond of DOPC and conclude that OBPC is an excellent structural isomorph for DOPC under the conditions of these experiments. The distribution obtained is the complete and fully resolved transbilayer image of the halogen label because the broad distribution of the bromines is due entirely to thermal disorder and not to experimental limitations [Wiener, M. C., & White, S. H. (1991a) Biophys. J. 59, 162-173]. The observed width of the bromine distribution indicates that virtually all of the hydrocarbon interior is accessible to the bromines. The distance between the bromine/double-bond position and the headgroup phosphate position was determined from one-dimensional Patterson maps and found to be approximately 12 A. The application of accurately determined bromine distributions to the quantitative interpretation of fluorescence quenching experiments is discussed. A method for the self-consistent global analysis of diffraction data from mixtures that permits the use of data sets with different instrumental scale factors is developed in an Appendix.